Measurement of Blood Glucose-Lowering and Antidiabetic Activity

  • Günter Müller
Living reference work entry


The rabbit has been used since many years for standardization of insulin (see K.4.1). Therefore, it has been chosen as the primary screening model for screening of blood glucose-lowering compounds as well as for establishing time-response curves and relative activities (Bänder et al. 1969, Geisen 1988).


British Pharmacopoeia Scintillation Proximity Assay Glucose Clamp Technique Continuous Blood Glucose Monitoring Euglycemic Clamp Technique 
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References and Further Reading

Blood Glucose-Lowering Effect in Rabbits

  1. Bänder A, Pfaff W, Schmidt FH, Stork H, Schröder HG (1969a) Zur Pharmakologie von HB 419, einem neuen, stark wirksamen oralen Antidiabeticum. Arzneim Forsch/Drug Res 19:1363–1372Google Scholar
  2. Biological Assay of Insulin. British Pharmacopoeia (1988) vol II, Her Majesty’s Stationary Office, London, pp A168–A170Google Scholar
  3. Bristow AF, Gaines Das RE, Bangham DR (1988) World Health Organization. International standards for highly purified human, porcine and bovine insulins. J Biol Stand 16:165–178PubMedGoogle Scholar
  4. British Pharmacopoeia (1999) Vol I, The Stationery Office, London, pp 789–794Google Scholar
  5. European Pharmacopoeia (1980) 2nd edn, V.2.2.3. Assay of InsulinGoogle Scholar
  6. European Pharmacopoeia (1997) 3rd edn, Insulin, pp 1020–1022Google Scholar
  7. Fieller EC (1944) A fundamental formula in the statistics of biological assay, and some applications. Quart J Pharm Pharmacol 17:117–123Google Scholar
  8. Geisen K (1988a) Special pharmacology of the new sulfonylurea glimepiride. Arzneim Forsch/Drug Res 38:1120–1130Google Scholar
  9. Harrison GA, Lawrence RD, Marks HP, Dale HH (1925) The strength of insulin preparations: a comparison between laboratory and clinical measurements. Br Med J 2:1102–1105PubMedCentralPubMedGoogle Scholar
  10. Insulin assay (1990) Rabbit blood-sugar method. In: United States Pharmacopoeia XXII. The National Formulary XVII. United States Pharmacopoeial Convention, Inc., Rockville, MD, pp 1513–1514Google Scholar
  11. Kurtz TE, Link RF, Tukey JW, Wallace DL (1966) Correlation of ranges of orrelated deviates. Biometrika 53:191–197.PubMedGoogle Scholar
  12. Levene H (1960) Robust tests for equality of variances. In: Olkin I, Ghury SG, Hoeffding W, Madow WG, Mann HB (eds) Contributions to probability and statistics. Essays in honor of Harold Hotteling. Stanford University Press, Stanford, CA, pp 278–292Google Scholar
  13. Miller RG (1966) Simultaneous statistical inference. McGraw-Hill, New YorkGoogle Scholar
  14. Rafaelsen OJ, Lauris V, Renold AE (1965) Localized intraperitoneal action of insulin on rat diaphragm and epididymal adipose tissue in vivo. Diabetes 14:19–26PubMedGoogle Scholar
  15. Salehi C, Atanasov P, Yang SP, Wilkins E (1996) A telemetry-instrumentation system for long-term implantable glucose and oxygen sensors. Anal Lett 29:2289–2308Google Scholar
  16. Scheffé H (1959) The analysis of variance. Wiley, New YorkGoogle Scholar
  17. Shapiro SS, Wilk MB (1965) An analysis of variance test for normality (Complete samples). Biometrika 52:591–611Google Scholar
  18. Shults MC, Rhodes RK, Updike ST, Gilligan BJ, Reining WN (1994) A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors. IEEE Trans Biomed Eng 41:937–942PubMedGoogle Scholar
  19. Sidak Z (1967) Rectangular confidence regions for the means of multivariate normal distributions. J Am Stat Assoc 62:626–631Google Scholar
  20. Underhill LA, Dabbah R, Grady LT, Rhodes CT (1994) Alternatives to animal testing in the USP-NF: present and future. Drug Develop Ind Pharm 20:165–216Google Scholar
  21. USP 23 (1995) Design and analysis of biological assays. The United States Pharmacopeia, Rockville, MD, pp 1705–1715Google Scholar
  22. USP 23 (1995) Insulin assay. The United States Pharmacopeia, Rockville, MD, pp 1716–1717Google Scholar
  23. USP 24 (2000) Insulin assays. The United States Pharmacopeia. Rockville, MD, pp 1848–1849Google Scholar
  24. Young DAB (1967) A serum inhibitor of insulin action on muscle. I Its detection and properties. Diabetologia 3:287–298PubMedGoogle Scholar

Blood Glucose-Lowering Effect in Mice

  1. Biological Assay of Insulin (1988) British pharmacopoeia, vol II, Her Majesty’s Stationary Office, London, pp A168–A170Google Scholar
  2. Eneroth G, Åhlund K (1968) Biological assay of insulin by blood sugar determination in mice. Acta Pharm Suec 5:691–594Google Scholar
  3. Eneroth G, Åhlund K (1970a) A twin crossover method for bioassay of insulin using blood glucose levels in mice – a comparison with the rabbit method. Acta Pharm Suec 7:457–462PubMedGoogle Scholar
  4. Eneroth G, Åhlund K (1970b) Exogenous insulin and blood glucose levels in mice. Factors affecting the dose–response relationship. Acta Pharm Suec 7:491–500PubMedGoogle Scholar
  5. European Pharmacopeia (1980) 2nd edn, V.2.2.3. Assay of InsulinGoogle Scholar
  6. Hoffman WS (1937) A rapid photoelectric method for the determination of glucose in blood and urine. J Biol Chem 120:51–55Google Scholar
  7. Wertbestimmung von Insulin (1986) Deutsches Arzneibuch, 9. Ausgabe, Deutscher Apotheker Verlag Stuttgart, pp 50–52Google Scholar

Blood Glucose-Lowering Effect in Dogs

  1. Bänder A, Pfaff W, Schmidt FH, Stork H, Schröder HG (1969b) Zur Pharmakologie von HB 419, einem neuen, stark wirksamen oralen Antidiabeticum. Arzneim Forsch/Drug Res 19:1363–1372Google Scholar
  2. Geisen K (1988b) Special pharmacology of the new sulfonylurea glimepiride. Arzneim Forsch/Drug Res 38:1120–1130Google Scholar
  3. Geisen K, Reisig E, Härtel D (1981) Kontinuierliche Blutglucosemessung und Infusion bei wachen, frei beweglichen Hunden. Continuous blood glucose monitoring and infusion in freely mobile dogs. Res Exp Med (Berl) 179:103–111Google Scholar

Blood Glucose-Lowering Effect in Other Species

  1. Gill AM, Yen TT (1991a) Effects of ciglitazone on endogenous plasma islet amyloid polypeptide and insulin sensitivity in obese-diabetic viable yellow mice. Life Sci 48:703–710PubMedGoogle Scholar
  2. Sohda T, Momose Y, Meguro K, Kawamatsu Y, Sugiyama Y, Ikeda H (1990a) Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones. Arzneim Forsch/Drug Res 40:37–42Google Scholar

Euglycemic Clamp Technique

  1. Bryer-Ash M, Follett L, Hodges N, Wimalawansa S (1995) Amylin-mediated reduction in insulin sensitivity corresponds to reduced insulin receptor kinase activity in the rat in vivo. Metabolism 44:705–711PubMedGoogle Scholar
  2. Burnol A, Leturque A, Ferre P (1983) A method for quantifying insulin sensitivity in the anesthetized rat: the euglycemic insulin clamp technique coupled with isotopic measurement of glucose turnover. Reprod Nutr Dev 23:429–435PubMedGoogle Scholar
  3. Burvin R, Armoni M, Karnieli E (1994) In vivo insulin action in normal and streptozotocin-induced diabetic rats. Physiol Behav 56:1–6PubMedGoogle Scholar
  4. DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223PubMedGoogle Scholar
  5. Cheung A, Bryer-Ash M (1994) Modified method for the performance of glucose insulin clamp studies in conscious rats. J Pharmacol Toxicol Meth 31:215–220Google Scholar
  6. Finegood DT, Bergman RN, Vranic A (1987) Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled glucose infusates. Diabetes 36:914–924PubMedGoogle Scholar
  7. Gelardi NL, Cha CM, Oh W (1991) Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique. Pediatric Res 30:40–44Google Scholar
  8. Hirshman MF, Horton ES (1990) Glyburide increases insulin sensitivity and responsiveness in peripheral tissues of the rat as determined by the glucose clamp technique. Endocrinol 126:2407–2412Google Scholar
  9. Hulman S, Falkner B, Freyvogel N (1993) Insulin resistance in the conscious spontaneously hypertensive rat: euglycemic hyperinsulinemic clamp study. Metabolism 42:14–18PubMedGoogle Scholar
  10. Kraegen EW, James DE, Bennett SP, Chishol DJ (1983) In vivo insulin sensitivity in the rat determined by euglycemic clamp. Am J Physiol 245 (Endocrinol Metab 8):E1–E7Google Scholar
  11. Kraegen EW, James DE, Jenkins AB, Chisholm DJ (1985) Dose-response curves for in vivo sensitivity in individual tissues in rats. Am J Physiol; Endocrin Metab 11:E353–E362Google Scholar
  12. Lang CH (1992) Rates and tissue sites of noninsulin- and insulin-mediated glucose uptake in diabetic rats. Proc Soc Exp Biol Med 199:81–87PubMedGoogle Scholar
  13. Lee MK, Miles PDG, Khoursheed M, Gao KM, Moossa AR, Olefsky JM (1994a) Metabolic effects of troglitazone on fructose-induced insulin resistance in rats. Diabetes 43:1435–1439PubMedGoogle Scholar
  14. Marfaing P, Ktorza A, Berthault MF, Predine J, Picon L, Penicaud L (1991) Effects of counterregulatory hormones on insulin-induced glucose utilization by individual tissues in rats. Diabete and Metabolisme (Paris) 17:55–60Google Scholar
  15. Ohsawa I, Sato J, Oshida Y, Sato Y, Sakamoto N (1991) Effect of glimepiride on insulin action in peripheral tissues of the rat determined by the euglycemic clamp technique. J Japan Diab Soc 34:873–874Google Scholar
  16. Tominaga M, Matsumoto M, Igarashi M, Eguchi H, Sekikawa A, Sasaki H (1992) Insulin antibody does not cause insulin resistance during glucose clamping in rats. Diabet Res Clin Pract 18:143–151Google Scholar
  17. Tominaga M, Igarashi M, Daimon M, Eguchi H, Matsumoto M, Sekikawa A, Yamatani K, Sasaki H (1993a) Thiazolidinediones (AD-4833 and CS-045) improve hepatic insulin resistance in streptozotocin-induced diabetic rats. Endocr J 40:343–349PubMedGoogle Scholar
  18. Xie H, Zhu L, Zhang YL, Legare DJ, Lautt WW (1996) Insulin sensitivity test with a modified euglycemic technique in cats and rats. J Pharmacol Toxicol Methods 35:77–82PubMedGoogle Scholar

Hypoglycemic Seizures in Mice

  1. Biological Assay of Insulin (1988) British Pharmacopoeia, vol II, Her Majesty’s Stationary Office, London, pp A168–A170Google Scholar
  2. British Pharmacopoeia (1999) Vol I, The Stationery Office, London, pp 789–794Google Scholar
  3. European Pharmacopeia (1980) 2nd edn, V.2.2.3. Assay of InsulinGoogle Scholar
  4. European Pharmacopoeia (1997) 3rd edn, Insulin, pp 1020–1022Google Scholar
  5. Fraser DT (1923) White mice and the assay of insulin. J Lab Clin Med 8:425–428Google Scholar
  6. Hemmingsen AM, Krogh A (1926) The assay of insulin by the convulsive-dose method on white mice. In: League of Nations; Health Organisation; The biological standardisation of insulin. Publications of The League of Nations. III. Health, 1926, III. 7. pp 40–46Google Scholar
  7. Litchfield JT, Wilcoxon F (1949) A simplified method for evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99PubMedGoogle Scholar
  8. Stewart GA (1974) Historical review of the analytical control of insulin. Analyst 99:913–928PubMedGoogle Scholar
  9. Trethewey J (1989) Bioassays for the analysis of insulin. J Pharm Biomed Anal 7:189–197PubMedGoogle Scholar
  10. Trevan JW, Boock E (1926) The standardisation of insulin by the determination of the convulsive dose for mice. In: League of Nations; Health organisation; The biological standardisation of insulin. Publications of the League of Nations. III. Health, 1926, III. 7. pp 47–56Google Scholar
  11. Wertbestimmung von Insulin. Deutsches Arzneibuch, 9. Ausgabe 1986, Deutscher Apotheker Verlag Stuttgart, pp 50–52Google Scholar
  12. Young DM, Lewis AH (1947) Detection of hypoglycemic reactions in the mouse assay for insulin. Science 105:368–369PubMedGoogle Scholar

Effects of Insulin Sensitizer Drugs

  1. Apweiler R, Kuhnle HF, Ritter G, Schell R, Freund P (1995) Effect of the nee antidiabetic agent (−)-BM 13.0913. Na on insulin resistance in lean and obese Zucker rats. Metabolism 44:577–583PubMedGoogle Scholar
  2. Bader S, Kiehn R, Häring HU (1993) Effekt von CS 045 auf die Kinaseaktivität des Insulinrezeptors im Skelettmuskel insulin-resistenter Zucker-Ratten. Diab Stoffw 2:56–61Google Scholar
  3. Chang AY, Wyse BM, Gilchrist BJ, Peterson T, Diani AR (1983) Ciglitazone, a new hypoglycemic agent. I: Studies in ob/ob and db/db mice, diabetic Chinese hamsters, and normal and streptozotocin-diabetic rats. Diabetes 32:830–838PubMedGoogle Scholar
  4. Ciaraldi TP, Gilmore A, Olefsky JM, Goldberg M, Heidenreich KA (1990) In vitro studies on the action of CS-045, a new antidiabetic agent. Metabolism 39:1056–1062PubMedGoogle Scholar
  5. Colca JR (1995) Insulin sensitiser drugs in development for the treatment in diabetes. Expert Opin Invest Drugs 4:27–29Google Scholar
  6. Diani AR, Peterson T, Samada GA, Wyse BM, Gilchrist BJ, Chang AY (1984) Ciglitazone, a new hypoglycemic agent. 4. Effects on pancreatic islets of C5BL/6 J-ob/ob and C57BL/KsJ-db/db mice. Diabetologia 27:225–234PubMedGoogle Scholar
  7. Fujita T, Sugiyama Y, Taketomi S, Sohda T, Kawamatsu Y, Iwatsuka H, Suzuki Z (1983) Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thizolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent. Diabetes 32:804–810PubMedGoogle Scholar
  8. Fujiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H (1988) Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes 37:1549–1558PubMedGoogle Scholar
  9. Fujiwara T, Wada M, Fukuda K, Fukami M, Yoshioka S, Yoshioka T, Horikoshi H (1991) Characterization of CS-045, a new oral antidiabetic agent, II. Effects on glycemic control and pancreatic islet structure at a late stage of the diabetes syndrome in C57BL/KsJ-db/db mice. Metabolism 40:1213–1218PubMedGoogle Scholar
  10. Fujiwara T, Akuno A, Yoshioka S, Horikoshi H (1995) Suppression of hepatic gluconeogenesis in long-term troglitazone treated diabetic KK and C57BL/ksJ-db/db mice. Metabolism 44:486–490PubMedGoogle Scholar
  11. Gill AM, Yen TT (1991b) Effects of ciglitazone on endogenous plasma islet amyloid polypeptide and insulin sensitivity in obese-diabetic viable yellow mice. Life Sci 48:703–710PubMedGoogle Scholar
  12. Hofmann C, Lorenz K, Colca JR (1991) Glucose transport deficiency in diabetic animals is corrected by treatment with the oral antihyperglycemic agent pioglitazone. Endocrinol 129:1915–1925Google Scholar
  13. Hofmann CA, Edwards CW, Hillman RM, Colca JR (1992) Treatment of insulin-resistant mice with the oral antidiabetic agent pioglitazone: evaluation of liver GLUT2 and phosphoenolpyruvate carboxykinase expression. Endocrinol 130:735–740Google Scholar
  14. Ikeda H, Taketomi S, Sugiyama Y, Shimura Y, Sohda T, Meguro K, Fujita T (1990) Effects of pioglitazone on glucose and lipid metabolism in normal and insulin resistant animals. Arzneim Forsch/Drug Res 40:156–162Google Scholar
  15. Kellerer M, Kroder G, Tippmer S, Berti L, Kiehn R, Mosthaf L, Häring H (1994) Troglitazone prevents glucose-induced insulin resistance of insulin receptor in rat-1 fibroblasts. Diabetes 43:447–453PubMedGoogle Scholar
  16. Kirsch DM, Bachmann W, Häring HU (1984) Ciglitazone reverses cAMP-induced post-insulin receptor resistance in rat adipocytes in vitro. FEBS Lett 176:49–54PubMedGoogle Scholar
  17. Kobayashi M, Iwanshi M, Egawa K, Shigeta Y (1992) Pioglitazone increases insulin sensitivity by activating insulin receptor kinase. Diabetes 41:476–483PubMedGoogle Scholar
  18. Kreutter DK, Andrews KM, Gibbs EM, Hutson NJ, Stevenson RW (1990) Insulin-like activity of new antidiabetic agent CP 68722 in 3 T3-L1 adipocytes. Diabetes 39:1414–1419PubMedGoogle Scholar
  19. Kuehnle HF (1996) New therapeutic agents for the treatment of NIDDM. Exp Clin Endocrinol Diabetes 104:93–101PubMedGoogle Scholar
  20. Lee MK, Olefsky JM (1995) Acute effects of troglitazone on in vivo insulin action in normal rats. Metabolism 44:1166–1169PubMedGoogle Scholar
  21. Lee MK, Miles PDG, Khoursheed M, Gao KM, Moossa AR, Olefsky JM (1994b) Metabolic effects of troglitazone on fructose-induced insulin resistance in rats. Diabetes 43:1435–1439PubMedGoogle Scholar
  22. Masuda K, Okamoto Y, Tuura Y, Kato S, Miura T, Tsuda K, Horikoshi H, Ishida H, Seino Y (1995) Effects of troglitazone (CS-045) on insulin secretion in isolated rat pancreatic islets and HIT cells: an insulinotropic mechanism distinct from glibenclamide. Diabetologia 38:24–30PubMedGoogle Scholar
  23. Murano K, Inoue Y, Emoto M, Kaku K, Kaneko T (1994) CS-045, a new oral antidiabetic agent, stimulates fructose-2,6-bisphosphate production in rat hepatocytes. Eur J Pharmacol 254:257–262PubMedGoogle Scholar
  24. Sohda T, Momose Y, Meguro K, Kawamatsu Y, Sugiyama Y, Ikeda H (1990b) Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones. Arzneim Forsch/Drug Res 40:37–42Google Scholar
  25. Stevenson RW, Hutson NJ, Krupp MN, Volkmann RA, Holland GF, Eggler JF, Clark DA, McPherson RK, Hall KL, Danbury BH, Gibbs EM, Kreutter DK (1990) Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice. Diabetes 39:1218–1227PubMedGoogle Scholar
  26. Stevenson RW, McPherson RK, Genereux PE, Danbury BH, Kreutter DK (1991) Antidiabetic agent englitazone enhances insulin action in nondiabetic rats without producing hypoglycemia. Metabolism 40:1268–1274PubMedGoogle Scholar
  27. Sugiyama Y, Taketomi S, Shimura Y, Ikeda H, Fujita T (1990) Effects of pioglitazone on glucose and lipid metabolism in Wistar fatty rats. Arzneim Forsch/Drug Res 40:263–267Google Scholar
  28. Tafuri SR (1996) Troglitazone enhances differentiation, glucose uptake, and Glut1 protein levels in 3 T3-L1 adipocytes. Endocrinology 137:4706–4712PubMedGoogle Scholar
  29. Teboul L, Gaillard D, Staccini L, Inadera H, Amri EZ, Grimaldi PA (1995) Thiazolidinediones and fatty acids convert myogenic cells into adipose-like cells. J Biol Chem 270:28183–28187PubMedGoogle Scholar
  30. Tominaga M, Igarashi M, Daimon M, Eguchi H, Matsumoto M, Sekikawa A, Yamatani K, Sasaki H (1993b) Thiazolidinediones (AD-4833 and CS-045) improve hepatic insulin resistance in streptozotocin-induced diabetic rats. Endocr J 40:343–349PubMedGoogle Scholar
  31. Yoshioka S, Nishino H, Shiraki T, Ikeda K, Koike H, Okuno A, Wada M, Fujiwara T, Horikoshi H (1993) Antihypertensive effects of CS-045 treatment in obese Zucker rats. Metabolism 42:75–80PubMedGoogle Scholar

Effects of Thiazolidinediones on Peroxisome Proliferator-Activated Receptor-γ

  1. Allan GF, Xiaohua L, Tsai SY, Weigel NL, Edwards DP, Tsai MJ, O’Malley BW (1992) Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation. J Biol Chem 267:19513–19520PubMedGoogle Scholar
  2. Berger A (2001) Resistin, a new hormone that links obesity with type 2 diabetes. Br Med J 322:193Google Scholar
  3. Berger J, Bailey P, Biswas C, Cullinan CA, Dobber TW, Hayes NS, Saperstein R, Smith RG, Leibowitz MD (1996) Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-γ: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology 137:4189–4195PubMedGoogle Scholar
  4. Berger J, Leibowitz MD, Doebber TW, Elbrecht A, Zhang B, Zhou G, Biswas C, Cullinan CA, Hayes NS, Li Y, Tanen M, Ventre J, Wu MS, Berger DG, Mosley R, Maequis R, Santini C, Sahoo SP, Tolman RL, Smith RG, Moller DE (1999) Novel peroxisome proliferator-activated receptor (PPAR)γ and PPARδ ligands produce distinct biological effects. J Biol Chem 274:6718–6726PubMedGoogle Scholar
  5. Brown PJ, Stuart WL, Hurley KP, Lewis MC, Winegar DA, Wilson JG, Wilkison WO, Ittoop OR, Willson TM (2001) Identification of a subtype selective human PPARα agonist through parallel-array synthesis. Bioorgan Med Chem Lett 11:1225–1227Google Scholar
  6. Brun RP, Kim JB, Hu E, Altiok S, Spiegelman BM (1996) Adipocyte differentiation: a transcriptional regulatory cascade. Curr Opin Cell Biol 8:826–832PubMedGoogle Scholar
  7. Choi KC, Ryu OH, Lee KW, Kim HY, Seo JA, Kim SG, Kim NH, Choi DS, Baik SH, Choi KM (2005) Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats. Biochem Biophys Res Commun 336:747–53PubMedGoogle Scholar
  8. De Vos P, Lefebre AM, Miller SG, Guerre-Millo M, Wong K, Saladin R, Hamann LG, Briggs MR, Auwerx J (1996) Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor-γ. J Clin Invest 98:49Google Scholar
  9. Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20:649–688PubMedGoogle Scholar
  10. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli E (1996) The PPARα-leukotriene B4 pathway to inflammation control. Nature 384:39–43PubMedGoogle Scholar
  11. Do D, Alvarez J, Chiquette E, Chilton R (2006) The good fat hormone: adiponectin and cardiovascular disease. Curr Atheroscler Rep 8:94–99PubMedGoogle Scholar
  12. Elbrecht A, Chen Y, Adams A, Berger J, Griffin P, Klatt T, Zhang B, Menke J, Zhou G, Smith RG, Moller DE (1999) L-764406 is a partial agonist of human peroxisome proliferator-activated receptor γ. J Biol Chem 274:7913–7922PubMedGoogle Scholar
  13. Forman BM, Totonoz P, Chen J, Brun RP, Spiegelman PE, Evans RM (1995) 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83:803–812PubMedGoogle Scholar
  14. Green S (1995) PPAR: a mediator of peroxisome proliferator action. Mutation Res 333:101–109PubMedGoogle Scholar
  15. Henke BR, Blanchard SG, Brackeen MF, Brown KK, Cobb JE, Collins JL, Harrington WW, Hashim MA, Hull-Ryde EA, Kaldor I, Kliewer SA, Lake DSH, Leesnitzer LM, Lehmann JM, Lenhard JM, Orband-Miller LA, Miller JF, Mook RA, Noble SA, Oliver W, Parks DJ, Plunket KD, Szewczyk JR, Willson TM (1998) N-(2-Benzoylphenyl)-L-tyrosine PPARγ agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents. J Med Chem 41:5020–5036PubMedGoogle Scholar
  16. Hollons T, Yoshimura FK (1989) Variation in enzymatic transient gene expression assays. Anal Biochem 182:411–418Google Scholar
  17. Keller H, Wahli W (1993) Peroxisome proliferator-activated receptors. A link between endocrinology and nutrition? Trends Endocrinol Metab 4:291–296PubMedGoogle Scholar
  18. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GP, Knoble SS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proc Natl Acad Sci U S A 94:4318–4323PubMedCentralPubMedGoogle Scholar
  19. Lee CH, Olson P, Evans RM (2003) Minireview: lipid metabolism, metabolic disorders and peroxisome proliferator-activated receptors. Endocrinology 144:2201–2207PubMedGoogle Scholar
  20. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ). J Biol Chem 270:121953–12956Google Scholar
  21. Lemberger T, Desvergne B, Wahli W (1996) Peroxisome proliferator–activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol 12:335–363PubMedGoogle Scholar
  22. Lin Q, Ruuska SE, Shaw NS, Dong D, Noy N (1999) Ligand selectivity of the peroxisome proliferator-activated receptor α. Biochemistry 38:185–190PubMedGoogle Scholar
  23. Lowell BB (1999) Minireview. An essential regulator of adipogenesis and modulator of fat cell function: PPARγ. Cell 99:239–242PubMedGoogle Scholar
  24. Matsusue K, Haluzik M, Lambert G, Yim SH, Gavrilova O, Ward JM, Brewer B, Reitman ML, Gonzalez FJ (2003) Liver-specific disruption of PPARγ in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest 111:737–747PubMedCentralPubMedGoogle Scholar
  25. Murakami K, Tobe K, Die T, Mochizuki T, Ohashi M, Akanuma Y, Yazaki Y, Kadowaki T (1998) A novel insulin sensitizer acts a coligand for peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ. Effect of PPAR-α activation on abnormal lipid metabolisms in liver of Zucker fatty rats. Diabetes 47:1841–1847PubMedGoogle Scholar
  26. Murphy GJ, Holder JC (2000) PPAR-γ agonists: therapeutic role in diabetes, inflammation and cancer. Trends Pharmacol Sci 21:469–474PubMedGoogle Scholar
  27. Nichols JS, Parks DJ, Consler TG, Blanchard SG (1998) Development of a scintillation proximity assay for peroxisome proliferators-activated γ ligand binding domain. Anal Biochem 257:112–119PubMedGoogle Scholar
  28. Norris AW, Chen L, Fisher SJ, Szanto I, Ristow M, Jozsi AC, Hirshman MF, Rosen ED, Goodyear LJ, Gonzalez FJ, Spiegelman BM, Kahn RC (2003) Muscle-specific PPARγ-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidines. J Clin Invest 112:608–618PubMedCentralPubMedGoogle Scholar
  29. Ram VJ (2003) Therapeutic significance of peroxisome proliferator-activated receptor modulators in diabetes. Drugs Today (Barc) 39:609–632Google Scholar
  30. Reginato MJ, Bailey ST, Krakow SL, Minami C, Ishii S, Tanaka H, Lazar MA (1998) A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor γ-activating properties. J Biol Chem 273:32679–32684PubMedGoogle Scholar
  31. Ribon V, Johnson JH, Camp HS, Saltiel AR (1998) Thiazolidinediones and insulin resistance: peroxisome proliferator-activated receptor γ activation stimulates expression of the CAP gene. Proc Natl Acad Sci U S A 95:14751–14756PubMedCentralPubMedGoogle Scholar
  32. Schoonjans K, Staels B, Auwerx J (1996a) The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochem Biophys Acta 1302:93–109PubMedGoogle Scholar
  33. Schoonjans K, Staels B, Auwerx J (1996b) Role of the peroxisome proliferator activated receptor (PPAR) in mediating effects of fibrates and fatty acids on gene expression. J Lipid Res 37:907–925PubMedGoogle Scholar
  34. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J (1996c) PPARα and PPARγ activators direct a distinct tissue-specific transcriptional response via the PPRE in the lipoprotein lipase gene. EMBO J 15:5336–5348PubMedCentralPubMedGoogle Scholar
  35. Schoonjans K, Martin G, Staels B, Auwerx J (1997) Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol 8:159–166PubMedGoogle Scholar
  36. Stanley TB, Leesnitzer LM, Montana VG, Galardi CM, Lambert MH, Holt JA, Xu HE, Moore LB, Blanchard SG, Stimmel JB (2003) Subtype specific effects of peroxisome proliferator-activated receptor ligands on corepressor activity. Biochemistry 42:9278–9287PubMedGoogle Scholar
  37. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312PubMedGoogle Scholar
  38. Stumvoll M (1998) Troglitazone. Diab Stoffw 7:136–143Google Scholar
  39. Su JL, Winegar DA, Wisely GB, Sigel CS, Hull-Ryde EA (1999) Use of PPAR gamma-specific monoclonal antibody to demonstrate thiazolidinediones induce PPAR gamma receptor expression in vitro. Hybridoma 18:273–280PubMedGoogle Scholar
  40. Tilley WD, Marcelli M, Wilson JD, McPhaul MJ (1989) Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci U S A 86:327–331PubMedCentralPubMedGoogle Scholar
  41. Tortonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 30:1147–1156Google Scholar
  42. Tortonoz P, Hu E, Spiegelman BM (1995) Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor γ. Curr Opin Genet Devel 5:571–576Google Scholar
  43. Vázquez M, Silvesatre JS, Prous JR (2002) Experimental approaches to study PPARγ agonists as antidiabetic drugs. Methods Find Exp Clin Pharmacol 24:515–523PubMedGoogle Scholar
  44. Vikramadithyan RK, Hiriyan J, Suresh J, Gershome C, Babu RK, Misra P, Rajagopalan CR (2003) DRF 2655: a unique molecule that reduces body weight and ameliorates metabolic abnormalities. Obesity Res 11:292–303Google Scholar
  45. Walczak R, Tontonoz P (2002) PPARadigms and PPARadoxes: expanding roles for PPARγ in the control of lipid metabolism. J Lipid Res 43:177–186PubMedGoogle Scholar
  46. Willson TM, Brown PJ, Sternbach DD, Henke BR (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem 43:527–550PubMedGoogle Scholar
  47. Wu Z, Xie Y, Morrison RF, Bucher NLR, Farmer SR (1998) PPAR-γ induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPα during the conversion of 3 T3 fibroblasts into adipocytes. J Clin Invest 101:22–32PubMedCentralPubMedGoogle Scholar
  48. Wurch T, Junquero D, Delhon A, Pauwels PJ (2002) Pharmacological analysis of wild-type α, γ and δ subtypes of the human peroxisome proliferator-activated receptor. Naunyn-Schmiedebergs Arch Pharmacol 365:133–140PubMedGoogle Scholar
  49. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe RT, Mc-Kee DD, Moore JT, Willson TM (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 98:13919–13924PubMedCentralPubMedGoogle Scholar
  50. Young PW, Buckle DR, Cantello BCC, Chapman H, Clapham JC, Coyle PJ, Haigh D, Hindley RM, Holder JC, Kallender H, Latter AJ, Lawrie KWM, Mossakowska D, Murphy GJ, Cox LR, Smith SA (1998) Identification of high-affinity binding sites for the insulin sensitizer Rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor γ. J Pharmacol Exp Ther 284:751–759PubMedGoogle Scholar

Antidiabetic Effects of Liver X Receptor Agonists

  1. Burris TP, Pelton PD, Zhou L, Osborne MC, Cryan E, Demarest KT (1999) A novel method for analysis of nuclear receptor function at natural promoters: Peroxisome proliferators-activated receptor γ agonist actions on aP2 gene expression detected using branch DNA messenger RNA quantification. Mol Endocrinol 13:410–417PubMedGoogle Scholar
  2. Cao G, Beyer TP, Yang XP, Schmidt RJ, Zhang Y, Bensch WR, Kauffman RF, Gao H, Ryan TP, Liang Y, Eacho PI, Jiang XC (2002) Phospholipid transfer protein is regulated by liver X receptors in vivo. J Biol Chem 277:39561–39565PubMedGoogle Scholar
  3. Cao G, Yu L, Broderick CL, Oldham BA, Beyer TP, Schmidt RJ, Zhang Y, Stayrook KR, Suen C, Otto KA, Miller AR, Dai J, Foxworthy P, Gao H, Ryan TP, Jiang XC, Burris TP, Eacho PI, Etgen GJ (2003) Antidiabetic action of a liver X receptor agonist mediated by inhibition of hepatic gluconeogenesis. J Biol Chem 278:1131–1136PubMedGoogle Scholar
  4. Chisholm JW, Hong J, Mills SA, Lawn RM (2003) The LXR ligand T0901317 induces severe lipogenesis in db/db diabetic mouse. J Lipid Res 44:2039–2048PubMedGoogle Scholar
  5. Goldman MJ, Back DW, Goodridge AG (1985) Nutritional regulation of the synthesis and degradation of malic enzyme messenger RNA in duck liver. J Biol Chem 260:4404–4408PubMedGoogle Scholar
  6. Mauvieux L, Canioni D, Hermine O, Valensi F, Radford-Weiss I, Azagury M, Magen M, Flandrin G, Brousse N, Varet B, Macintyre EA (1998) Quantitative RNA slot-blot analysis of CCND1/cyclin D1 expression in suspected mantle cell lymphomas. Leukemia 12:78–85PubMedGoogle Scholar
  7. Mukherjee R, Davies PJ, Crombie DL, Bischoff ED, Cesaario RM, Jow L, Hamann LG, Boem MF, Mondon CE, Nadzan AM, Paterniti JR, Heyman RA (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 386:407–410PubMedGoogle Scholar
  8. Schibler U, Hagenbuchle O, Wellauer PK, Pittet AC (1983) Two promoters of different strength control the transcription of the mouse α-amylase gene Amy-1a in the parotid gland and the liver. Cell 32:501–508Google Scholar
  9. Steffensen KR, Gustafsson JÅ (2004) Putative metabolic effects of the liver X receptor (LXR). Diabetes 53(Suppl 1):S36–S42PubMedGoogle Scholar
  10. Stulnig TM, Oppermann U, Steffensen KR, Schuster GU, Gustafsson JÅ (2002a) Liver X receptors downregulate 11β-hydroxysteroid dehydrogenase type 1 expression and activity. Diabetes 51:2426–2433PubMedGoogle Scholar
  11. Stulnig TM, Steffensen KR, Gao H, Reimers M, Dahlman-Wright K, Schuster GU, Gustafsson JÅ (2002b) Novel roles of liver X receptors exposed by gene expression profiling in liver and adipose tissue. Mol Pharmacol 62:1299–1305PubMedGoogle Scholar

Measurement of Energy Metabolism

  1. Ader DN, Johnson SB, Huang SW, Riley WJ (1991) Group size, cage shelf level, and emotionality in non-obese diabetic mice: impact on onset and incidence of IDDM. Psychosom Med 53:313–321PubMedGoogle Scholar
  2. Allison DB, Paultre F, Goran MI, Poehlman ET, Heymsfield SB (1995) Statistical considerations regarding the use of ratios to adjust data. Int J Obes Relat Metab Disord 19:644–652PubMedGoogle Scholar
  3. Almind K, Kahn CR (2004) Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Diabetes 53:3274–3285PubMedGoogle Scholar
  4. Arch JR, Hislop D, Wang SJ, Speakman JR (2006) Some mathematical and technical issues in the measurement and interpretation of open-circuit indirect calorimetry in small animals. Int J Obes Relat Metab Disord 30:1322–1331Google Scholar
  5. Arndt SS et al (2009) Individual housing of mice–impact on behaviour and stress responses. Physiol Behav 97:385–393PubMedGoogle Scholar
  6. Bartolomucci A (2007) Social stress, immune functions and disease in rodents. Front Neuroendocrinol 28:28–49PubMedGoogle Scholar
  7. Bartolomucci A et al (2009) Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress. PLoS One 4, e4331PubMedCentralPubMedGoogle Scholar
  8. Bartolomucci A et al (2004) Age at group formation alters behavior and physiology in male but not female CD-1 mice. Physiol Behav 82:425–434PubMedGoogle Scholar
  9. Brown JH, Gillooly JF, Allen AP, Savage VM, West GB (2004) Toward a metabolic theory of ecology. Ecology 85:1771–1789Google Scholar
  10. Butler AA, Kozak LP (2010) A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 59:323–329PubMedCentralPubMedGoogle Scholar
  11. Champy MF et al (2008) Genetic background determines metabolic phenotypes in the mouse. Mamm Genome 19:318–331PubMedGoogle Scholar
  12. Champy MF et al (2004) Mouse functional genomics requires standardization of mouse handling and housing conditions. Mamm Genome 15:768–783PubMedGoogle Scholar
  13. Cohn DWH, Sa-Rocha LC (2009) Sickness and aggressive behavior in dominant and subordinate mice. Ethology 115:112–121Google Scholar
  14. Daan S, Masman D, Groenewold A (1990) Avian basal metabolic rates – their association with body-composition and energy-expenditure in nature. Am J Physiol 259:R333–R340PubMedGoogle Scholar
  15. Dahlin J et al (2009) Body weight and faecal corticosterone metabolite excretion in male Sprague–Dawley rats following short transportation and transfer from group-housing to single-housing. Scand J Lab Anim Sci 36:205–213Google Scholar
  16. Elia M (1992) Organ and tissue contribution to metabolic rate. In: Elia M, Kinney JM, Tucker HN (eds) Energy metabolism: tissue determinants and cellular corollaries. Raven, New York, NY, pp 61–80Google Scholar
  17. Faber P, Lammert O, Johansen O, Garby L (1998) A fast responding combined direct and indirect calorimeter for human subjects. Med Eng Phys 20:291–301PubMedGoogle Scholar
  18. Gallagher D et al (2006) Small organs with a high metabolic rate explain lower resting energy expenditure in African American than in white adults. Am J Clin Nutr 83:1062–1067PubMedCentralPubMedGoogle Scholar
  19. Gallagher D et al (1998) Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass. Am J Physiol-Endocrinol Metab 38:E249–E258Google Scholar
  20. Guo J, Hall KD (2009) Estimating the continuous-time dynamics of energy and fat metabolism in mice. PLoS Comput Biol 5, e10005111Google Scholar
  21. Heymsfield SB et al (2002) Body-size dependence of resting energy expenditure can be attributed to nonenergetic homogeneity of fat-free mass. Am J Physiol-Endocrinol Metab 282:E132–E138PubMedGoogle Scholar
  22. Hunt C, Hambly C (2006) Faecal corticosterone concentrations indicate that separately housed male mice are not more stressed than group housed males. Physiol Behav 87:519–526PubMedGoogle Scholar
  23. Johnstone AM, Murison SD, Duncan JS, Rance KA, Speakman JR (2005) Factors influencing variation in basal metabolic rate include fat-free mass, fat mass, age, and circulating thyroxine but not sex, circulating leptin, or triiodothyronine. Am J Clin Nutr 82:941–948PubMedGoogle Scholar
  24. Kaiyala KJ, Schwartz MW (2011) Toward a more complete (and less controversial) understanding of energy expenditure and its role in obesity pathogenesis. Diabetes 60:17–23PubMedCentralPubMedGoogle Scholar
  25. Kaiyala KJ et al (2010) Identification of body fat mass as a major determinant of metabolic rate in mice. Diabetes 59:1657–1666PubMedCentralPubMedGoogle Scholar
  26. Kleiber M (1932) Body size and metabolism. Hilgardia 6:315–353Google Scholar
  27. Kleiber M (1961) The fire of life: an introduction to animal energetics. Wiley and Co, New YorkGoogle Scholar
  28. Kolokotrones T, Savage V, Deeds EJ, Fontana W (2010) Curvature in metabolic scaling. Nature 464:753–756PubMedGoogle Scholar
  29. Konarzewski M, Diamond J (1995) Evolution of basal metabolic rate and organ masses in laboratory mice. Evolution 49:1239–1248Google Scholar
  30. Krebs HA (1950) Body size and tissue respiration. Biochim Biophys Acta 4:249–269PubMedGoogle Scholar
  31. Krol E, Murphy M, Speakman JR (2007) Limits to sustained energy intake. X. Effects of fur removal on reproductive performance in laboratory mice. J Exp Biol 210:4233–4243PubMedGoogle Scholar
  32. Levine JA (2005) Measurement of energy expenditure. Public Health Nutr 8:1123–1132PubMedGoogle Scholar
  33. Lifson N, Gordon GB, McClintock R (1955) Measurement of total carbon dioxide production by D2O18. J Appl Physiol 7:704–710PubMedGoogle Scholar
  34. Lifson N, McClintock R (1966) Theory of use of turnover rates of body water for measuring energy and material balance. J Theor Biol 12:46–74PubMedGoogle Scholar
  35. Martin AL, Brown RE (2010) The lonely mouse: verification of a separation-induced model of depression in female mice. Behav Brain Res 207:196–207PubMedGoogle Scholar
  36. Meyer CW et al (2007) Expanding the body mass range: associations between BMR and tissue morphology in wild type and mutant dwarf mice (David mice). J Comp Physiol B 177:183–192PubMedGoogle Scholar
  37. Moles A et al (2006) Psychosocial stress affects energy balance in mice: modulation by social status. Psychoneuroendocrinology 31:623–633PubMedGoogle Scholar
  38. Poehlman ET, Toth MJ (1995) Mathematical ratios lead to spurious conclusions regarding age-related and sex-related differences in resting metabolic-rate. Am J Clin Nutr 61:482–485PubMedGoogle Scholar
  39. Raichlen DA, Gordon AD, Muchlinski MN, Snodgrass JJ (2010) Causes and significance of variation in mammalian basal metabolism. J Comp Physiol B 180:301–311PubMedGoogle Scholar
  40. Ravussin E, Bogardus C (1989) Relationship of genetics, age, and physical fitness to daily energy-expenditure and fuel utilization. Am J Clin Nutr 49:968–975PubMedGoogle Scholar
  41. Reynolds DS, Kunz TH (2001) Standard methods for destructive body composition analysis. In: Speakman JR (ed) Body composition analysis of animals: a handbook of non-destructive methods. Cambridge University Press, Cambridge, UK, pp 39–55Google Scholar
  42. Rolfe DFS, Brown GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 77:731–758PubMedGoogle Scholar
  43. Rubner M (1883) Über den Einfluss der Körpergrösse auf Stoff- und Kraftwechsel. Z Biol 19:536–562Google Scholar
  44. Schmidt MV et al (2010) A novel chronic social stress paradigm in female mice. Horm Behav 57:415–420PubMedGoogle Scholar
  45. Schmidt MV et al (2007) Persistent neuroendocrine and behavioral effects of a novel, etiologically relevant mouse paradigm for chronic social stress during adolescence. Psychoneuroendocrinology 32:417–429PubMedGoogle Scholar
  46. Speakman JR (1997) Doubly-labelled water: theory and practice. Kluwer, DordrechtGoogle Scholar
  47. Speakman JR et al (2010) FTO effect on energy demand versus food intake. Nature 464:E1–E5PubMedGoogle Scholar
  48. Speakman JR, Hambly C (2007) Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan. J Nutr 137:1078–1086PubMedGoogle Scholar
  49. Speakman JR, Krol E (2010) Maximal heat dissipation capacity and hyperthermia risk: neglected key factors in the ecology of endotherms. J Anim Ecol 79:726–746PubMedGoogle Scholar
  50. Spinnler G, Jequier E, Favre R, Dolivo M, Vannotti A (1973) Human calorimeter with a new type of gradient layer. J Appl Physiol 35:158–165PubMedGoogle Scholar
  51. Tschöp MH, Speakman JR, Arch JR, Auwerx J, Brüning JC, Chan L, Eckel RH, Farese RV Jr et al (2011) A guide to analysis of mouse energy metabolism. Nat Methods 9:57–63PubMedCentralPubMedGoogle Scholar
  52. Virtanen KA et al (2009) Brief report: functional brown adipose tissue in healthy adults. N Engl J Med 360:1518–1525PubMedGoogle Scholar
  53. Wang ZM et al (2000) Resting energy expenditure-fat-free mass relationship: new insights provided by body composition modeling. Am J Physiol-Endocrinol Metab 279:E539–E545PubMedGoogle Scholar
  54. Wang ZM, Heshka S, Heymsfield SB, Shen W, Gallagher D (2005) A cellular-level approach to predicting resting energy expenditure across the adult years. Am J Clin Nutr 81:799–806PubMedGoogle Scholar
  55. Wang ZM, O’Connor TP, Heshka S, Heymsfield SB (2001) The reconstruction of Kleiber’s law at the organ-tissue level. J Nutr 131:2967–2970PubMedGoogle Scholar
  56. White CR, Blackburn TM, Seymour RS (2009) Phylogenetically informed analysis of the allometry of mammalian basal metabolic rate supports neither geometric nor quarter-power scaling. Evolution 63:2658–2667PubMedGoogle Scholar
  57. Woods SC, Schwartz MW, Baskin DG, Seeley RJ (2000) Food intake and the regulation of body weight. Annu Rev Psychol 51:255–277PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.HelmholtzZentrum MünchenHelmholtz Diabetes Center, Institute for Diabetes and ObesityMunichGermany

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