Skip to main content
SpringerLink
Log in

Rosiglitazone decreases fasting plasma peptide YY3–36 in type 2 diabetic women: a possible role in weight gain?

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Rosiglitazone often results in weight gain. We hypothesized that rosiglitazone may modulate circulating levels of ghrelin and peptide YY3–36 and this modulation may be related to weight-gaining effect of this agent. This study was designed as an open-label, randomized, controlled trial of 3-month duration. Women with newly diagnosed type 2 diabetes were studied. Twenty-eight of the 55 eligible participants were randomly assigned to receive rosiglitazone (4 mg/d). Twenty-seven patients with diabetes matched for age and body mass index served as controls on diet alone. We evaluated the effects of 3 months of rosiglitazone treatment on fasting peptide YY3–36 and ghrelin levels, and anthropometric measurements. The 3-month administration of rosiglitazone reduced fasting plasma peptide YY3–36 levels by 25%, the between-group difference was statistically significant. No effect of this thiazolidinedione compound on fasting ghrelin concentrations was observed at the end of study. The ghrelin/body mass index ratio also did not change significantly after treatment. Seventy-five percent of the women with diabetes complained of increased hunger at the end of study. Nevertheless, all subjects exhibited a decrease in fasting PYY levels after 3 months of rosiglitazone therapy, irrespective of the levels of hunger. There was no significant correlation between changes in peptide YY3–36 and those in anthropometric parameters and insulin sensitivity at the end of the study. Rosiglitazone-induced decrease in fasting peptide YY3–36 levels may in part contribute to orexigenic and weight-gaining effect of this thiazolidinedione derivative.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cummings DE, Overduin J (2007) Gastrointestinal regulation of food intake. J Clin Invest 117(1):13–23. doi:10.1172/JCI30227

    Article  PubMed  CAS  Google Scholar 

  2. Wynne K, Bloom SR (2006) The role of oxyntomodulin and peptide tyrosine–tyrosine (PYY) in appetite control. Nat Clin Pract Endocrinol Metab 2(11):612–620. doi:10.1038/ncpendmet0318

    Article  PubMed  CAS  Google Scholar 

  3. Baynes KC, Dhillo WS, Bloom SR (2006) Regulation of food intake by gastrointestinal hormones. Curr Opin Gastroenterol 22(6):626–631. doi:10.1097/01.mog.0000245537.43142.63

    Article  PubMed  CAS  Google Scholar 

  4. Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M (2004) Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J 18(3):439–456. doi:10.1096/fj.03-0641rev

    Article  PubMed  CAS  Google Scholar 

  5. Kojima M, Hosoda H, Date Y, Nakazato M, Kanagawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762):656–660. doi:10.1038/45230

    Article  PubMed  CAS  Google Scholar 

  6. Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, Witcher DR, Luo S, Onyia JE, Hale JE (2008) Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 105(17):6320–6325. doi:10.1073/pnas.0800708105

    Article  PubMed  CAS  Google Scholar 

  7. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL (2008) Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell 132(3):387–396. doi:10.1016/j.cell.2008.01.017

    Article  PubMed  CAS  Google Scholar 

  8. Kirchner H, Gutierrez JA, Solenberg PJ, Pfluger PT, Czyzyk TA, Willency JA, Schürmann A, Joost HG, Jandacek RJ, Hale JE, Heiman ML, Tschöp MH (2009) GOAT links dietary lipids with the endocrine control of energy balance. Nat Med 15(7):741–745. doi:10.1038/nm.1997

    Article  PubMed  CAS  Google Scholar 

  9. Kamegai J, Tamura H, Shimizu T, Ishii S, Suighara H, Wakabayashi I (2000) Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. Endocrinology 141(12):4797–4800. doi:10.1210/en.141.12.4797

    Article  PubMed  CAS  Google Scholar 

  10. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K (2001) Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes 50(2):227–232. doi:10.2337/diabetes.50.2.227

    Article  PubMed  CAS  Google Scholar 

  11. Zhang W, Zhao L, Lin TR, Chai B, Fan Y, Gantz I, Mulholland MW (2004) Inhibition of adipogenesis by ghrelin. Mol Biol Cell 15(5):2484–2491. doi:10.1091/mbc.E03-09-0657

    Article  PubMed  CAS  Google Scholar 

  12. Batterham RL, Bell JD, Chandarana K, Chivers JE, Heffron H, Herzog H, Kapoor S, Le Roux CW, Thomas EL, Withers DJ (2006) Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab 4(3):223–233. doi:10.1016/j.cmet.2006.08.001

    Article  PubMed  CAS  Google Scholar 

  13. Chelikani PK, Haver AC, Reidelberger RD (2004) Comparison of the inhibitory effects of PYY(3–36) and PYY(1–36) on gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 287(5):R1064–R1070. doi:10.1152/ajpregu.00376.2004

    Google Scholar 

  14. Keire DA, Mannon P, Kobayashi M, Walsh JH, Solomon TE, Reeve JR Jr (2000) Primary structures of PYY, [Pro(34)]PYY, and PYY-(3–36) confer different conformations and receptor selectivity. Am J Physiol Gastrointest Liver Physiol 279(1):G126–G131

    PubMed  CAS  Google Scholar 

  15. Popovic V, Duntas LH (2005) Brain somatic cross-talk: Ghrelin, leptin and ultimate challengers of obesity. Nutr Neurosci 8(1):1–5. doi:10.1080/10284150400027107

    Article  PubMed  CAS  Google Scholar 

  16. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR (2003) Inhibition of food intake in obese subjects by peptide YY3–36. N Engl J Med 349(10):941–948

    Article  PubMed  CAS  Google Scholar 

  17. 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 270:12953–12956. doi:10.1074/jbc.270.22.12953

    Article  PubMed  CAS  Google Scholar 

  18. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4(4):611–617. doi:10.1016/S1097-2765(00)80211-7

    Article  PubMed  CAS  Google Scholar 

  19. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14(11):1293–1307. doi:10.1101/gad.14.11.1293

    PubMed  CAS  Google Scholar 

  20. Fidan E, Onder Ersoz H, Yilmaz M, Yilmaz H, Kocak M, Karahan C, Erem C (2011) The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus. Acta Diabetol 23 Mar. [Epub ahead of print] PubMed PMID: 21424914. doi:10.1007/s00592-011-0276-y

  21. Wang AP, Li X, Zheng Y, Liu BL, Huang G, Yan X, Liu Z, Zhou Z (2010) Thiazolidinediones protect mouse pancreatic β-cells directly from cytokine-induced cytotoxicity through PPARγ-dependent mechanisms. Acta Diabetol 10 Dec. [Epub ahead of print] PubMed PMID: 21153483. doi:10.1007/s00592-010-0239-8

  22. Scheen AJ (2002) Glitazones and weight gain. Ann Endocrinol (Paris) 63:IS412–IS414

    Google Scholar 

  23. Hermansen K, Mortensen LS (2007) Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus. Drug Saf 30(12):1127–1142

    Article  PubMed  CAS  Google Scholar 

  24. Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain A, Atreja A, Zimmerman RS (2009) The risk of developing coronary artery disease or congestive heart failure, and overall mortality, in type 2 diabetic patients receiving rosiglitazone, pioglitazone, metformin, or sulfonylureas: a retrospective analysis. Acta Diabetol 46(2):145–154. doi:10.1007/s00592-008-0090-3

    Article  PubMed  CAS  Google Scholar 

  25. Lebovitz HE (2002) Differentiating members of the thiazolidinedione class: a focus on safety. Diabetes Metab Res Rev 18(Suppl 2):S23–S29. doi:10.1002/dmrr.252

    Article  PubMed  CAS  Google Scholar 

  26. Barnett AH (2002) Insulin-sensitizing agents-thiazolidinediones (glitazones). Curr Med Res Opin 18(Suppl 1):S31–S39

    Google Scholar 

  27. De Vos P, Lefebvre AM, Miller SG, Guerre-Millo M, Wong K, Saladin R, Hamann LG, Staels B, Briggs MR, Auwerx J (1996) Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma. J Clin Invest 98(4):1004–1009. doi:10.1172/JCI118860

    Article  PubMed  Google Scholar 

  28. Zhang B, Graziano MP, Doebber TW, Leibowitz MD, White-Carrington S, Szalkowski DM, Hey PJ, Wu M, Cullinan CA, Bailey P, Lollmann B, Frederich R, Flier JS, Strader CD, Smith RG (1996) Down-regulation of the expression of the obese gene by an antidiabetic thiazolidinedione in Zucker diabetic fatty rats and db/db mice. J Biol Chem 271(16):9455–9459. doi:10.1074/jbc.271.16.9455

    Article  PubMed  CAS  Google Scholar 

  29. Wang Q, Dryden S, Frankish HM, Bing C, Pickavance L, Hopkins D, Buckingham R, Williams G (1997) Increased feeding in fatty Zucker rats by the thiazolidinedione BRL 49653 (rosiglitazone) and the possible involvement of leptin and hypothalamic neuropeptide Y. Br J Pharmacol 122(7):1405–1410. doi:10.1038/sj.bjp.0701535

    Article  PubMed  CAS  Google Scholar 

  30. Larsen PJ, Jensen PB, Sørensen RV, Larsen LK, Vrang N, Wulff EM, Wassermann K (2003) Differential influences of peroxisome proliferator-activated receptors γ and -α on food intake and energy homeostasis. Diabetes 52(9):2249–2259. doi:10.2337/diabetes.52.9.2249

    Article  PubMed  CAS  Google Scholar 

  31. Shimizu H, Tsuchiya T, Sato N, Shimomura Y, Kobayashi I, Mori M (1998) Troglitazone reduces plasma leptin concentration but increases hunger in NIDDM patients. Diabetes Care 21(9):1470–1474. doi:10.2337/diacare.21.9.1470

    Article  PubMed  CAS  Google Scholar 

  32. American Diabetes Association (2001) Nutrition recommendations and principles for people with diabetes mellitus (Position Statement). Diabetes Care 24(Suppl 1):S44–S47

    Google Scholar 

  33. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β–cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419. doi:10.1007/BF00280883

    Article  PubMed  CAS  Google Scholar 

  34. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR (2000) The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141(11):4325–4328. doi:10.1210/en.141.11.4325

    Article  PubMed  CAS  Google Scholar 

  35. Le Roux CW, Batterham RL, Aylwin SJ, Patterson M, Borg CM, Wynne KJ, Kent A, Vincent RP, Gardiner J, Ghatei MA, Bloom SR (2006) Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147(1):3–8. doi:10.1210/en.2005-0972

    Article  PubMed  CAS  Google Scholar 

  36. Korner J, Inabnet W, Conwell I-M, Taveras C, Daud A, Olivero-Rivera L, Restuccia NL, Bessler M (2006) Differential effects of gastric bypass and banding on circulating gut hormone and leptin levels. Obesity (Silver Spring) 14(9):1553–1561. doi:10.1038/oby.2006.179

    Article  CAS  Google Scholar 

  37. Guo Y, Ma L, Enriori PJ, Koska J, Franks PW, Brookshire T, Cowley MA, Salbe AD, Delparigi A, Tataranni PA (2006) Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans. Obesity (Silver Spring) 14(9):1562–1570. doi:10.1038/oby.2006.180

    Article  CAS  Google Scholar 

  38. Nakahara R, Kojima S, Tanaka M, Yasuhara D, Harada T, Sagiyama K, Muranaga T, Nagai N, Nakazato M, Nozoe S, Naruo T, Inui A (2007) Incomplete restoration of the secretion of ghrelin and PYY compared to insulin after food ingestion following weight gain in anorexia nervosa. J Psychiatr Res 41(10):814–820. doi:10.1016/j.jpsychires.2006.07.021

    Article  PubMed  Google Scholar 

  39. Pfluger PT, Kampe J, Castaneda T, Vahl T, D’Alessio DA, Kruthaupt T, Benoit SC, Cuntz U, Rochlitz HJ, Moehlig M, Pfeiffer AFH, Koebnick C, Weickert MO, Otto B, Spranger J, Tschop MH (2007) Effect of human body weight changes on circulating levels of peptide YY and peptide YY3–36. J Clin Endocrinol Metab 92(2):583–588. doi:10.1210/jc.2006-1425

    Article  PubMed  CAS  Google Scholar 

  40. Yildirim S, Bolkent S, Sundler F (2008) The role of rosiglitazone treatment in the modulation of islet hormones and hormone-like peptides: a combined in situ hybridization and immunohistochemical study. J Mol Histol 39(6):635–642. doi:10.1007/s10735-008-9204-z

    Article  PubMed  CAS  Google Scholar 

  41. Ali-Rachedi A, Varndell IM, Adrian TE, Gapp DA, Noorden SV, Bloom SR, Polak JM (1984) Peptide YY (PYY) immunoreactivity is co-stored with glucagon-related immunoreactants in endocrine cells of the gut and pancreas. Histochem Cell Biol 80(5):487–491. doi:10.1007/BF00495439

    Article  CAS  Google Scholar 

  42. Böttcher G, Sjöberg J, Ekman R, Hakanson R, Sundler F (1993) Peptide YY in the mammalian pancreas: immunocytochemical localization and immunochemical characterization. Regul Pept 43(3):115–130. doi:10.1016/0167-0115(93)90146-Y

    Article  PubMed  Google Scholar 

  43. Boggiano MM, Chandler PC, Oswald KD, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Schindler M, Arndt K, Rudolf K, Mark M, Schoelch C, Joost HG, Klaus S, Thone-Reineke C, Benoit SC, Seeley RJ, Beck-Sickinger AG, Koglin N, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Deng XY, Whitcomb DC, Halem H, Taylor J, Dong J, Datta R, Culler M, Ortmann S, Castaneda TR, Tschop M (2005) PYY3–36 as an anti-obesity drug target. Obes Rev 6(4):307–322. doi:10.1111/j.1467-789X.2005.00218.x

    Article  PubMed  CAS  Google Scholar 

  44. Tschop M, Castaneda TR, Joost HG, Thone-Reineke C, Ortmann S, Klaus S, Hagan MM, Chandler PC, Oswald KD, Benoit SC, Seeley RJ, Kinzig KP, Moran TH, Beck-sickinger AG, Koglin N, Rodgers RJ, Blundell JE, Ishii Y, Beattie AH, Holch P, Allison DB, Raun K, Madsen K, Wulff BS, Stidsen CE, Birringer M, Kreuzer OJ, Schindler M, Arndt K, Rudolf K, Mark M, Deng XY, Whitcomb DC, Halem H, Taylor J, Dong J, Datta R, Culler M, Craney S, Flora D, Smiley D, Heiman ML, Withcomb DC (2004) Physiology: does gut hormone PYY3–36 decrease food intake in rodents? Nature 430(6996):1. doi:10.1038/nature02665

  45. Menghini R, Marchetti V, Cardellini M, Hribal ML, Mauriello A, Lauro D, Sbraccia P, Lauro R, Federici M (2005) Phosphorylation of GATA2 by Akt increases adipose tissue differentiation and reduces adipose tissue-related inflammation: a novel pathway linking obesity to atherosclerosis. Circulation 111(15):1946–1953. doi:10.1161/01.CIR.0000161814.02942.B2

    Article  PubMed  CAS  Google Scholar 

  46. Majuri A, Santaniemi M, Rautio K, Kunnari A, Vartiainen J, Ruokonen A, Kesäniemi YA, Tapanainen JS, Ukkola O, Morin-Papunen L (2007) Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study. Eur J Endocrinol 156(2):263–269. doi:10.1530/eje.1.0233138

    Article  PubMed  CAS  Google Scholar 

  47. Kusaka I, Nagasaka S, Horie H, Ishibashi S (2008) Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability? Diabetes Obes Metab 10(11):1039–1046. doi:10.1111/j.1463-1326.2008.00857.x

    Article  PubMed  CAS  Google Scholar 

  48. Kadoglou NP, Tsanikidis H, Kapelouzou A, Vrabas I, Vitta I, Karayannacos PE, Liapis CD, Sailer N (2010) Effects of rosiglitazone and metformin treatment on apelin, visfatin, and ghrelin levels in patients with type 2 diabetes mellitus. Metabolism 59(3):373–379. doi: 10.1016/j.metabol.2009.08.005

    Google Scholar 

  49. Hutchinson DS, Summers RJ, Bengtsson T (2008) Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: potential utility in treatment of diabetes and heart disease. Pharmacol Ther 119(3):291–310. doi:10.1016/j.pharmthera.2008.05.008

    Article  PubMed  CAS  Google Scholar 

  50. Schimmack G, Defronzo RA, Musi N (2006) AMP-activated protein kinase: role in metabolism and therapeutic implications. Diabetes Obes Metab 8(6):591–602. doi:10.1111/j.1463-1326.2005.00561.x

    Article  PubMed  CAS  Google Scholar 

  51. Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M (2006) Expanding role of AMPK in endocrinology. Trends Endocrinol Metab 17(5):205–215. doi:10.1016/j.tem.2006.05.006

    Article  PubMed  CAS  Google Scholar 

  52. Kotani K, Sakane N, Saiga K, Adachi S, Mu H, Kurozawa Y, Kawano M (2006) Serum ghrelin and carotid atherosclerosis in older Japanese people with metabolic syndrome. Arch Med Res 37(7):903–906. doi:10.1016/j.arcmed.2006.03.004

    Article  PubMed  CAS  Google Scholar 

  53. Soeki T, Kishimoto I, Schwenke DO, Tokudome T, Horio T, Yoshida M, Hosoda H, Kangawa K (2008) Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. Am J Physiol Heart Circ Physiol 294(1):H426–H432. doi:10.1152/ajpheart.00643.2007

    Article  PubMed  CAS  Google Scholar 

  54. Xu X, Jhun BS, Ha CH, Jin ZG (2008) Molecular mechanisms of ghrelin-mediated endothelial nitric oxide synthase activation. Endocrinology 149(8):4183–4192. doi:10.1210/en.2008-0255

    Article  PubMed  CAS  Google Scholar 

  55. Iantorno M, Chen H, Kim JA, Tesauro M, Lauro D, Cardillo C, Quon MJ (2007) Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells. Am J Physiol Endocrinol Metab 292(3):E756–E764. doi:10.1152/ajpendo.00570.2006

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study has been submitted to www.clinicaltrials.gov (ID: NCT00522470). The authors have no duality of interest in regard to this study. The supporting source (Baskent University) had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report and in the decision to submit the report for publication.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Turkiye Yuksek Ihtisas Education and Research Hospital, Kızılay sokak, 06100, Sihhiye, Ankara, Turkey

    Zehra Berberoglu

  2. Department of Biostatistics, Faculty of Medicine, Baskent University, Ankara, Turkey

    Ayse Canan Yazici

  3. Department of Biochemistry, Faculty of Medicine, Baskent University, Ankara, Turkey

    Nilufer Bayraktar

  4. Department of Endocrinology and Metabolism, Faculty of Medicine, Baskent University, Ankara, Turkey

    Nilgun Guvener Demirag

Authors
  1. Zehra Berberoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayse Canan Yazici
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nilufer Bayraktar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nilgun Guvener Demirag
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zehra Berberoglu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berberoglu, Z., Yazici, A.C., Bayraktar, N. et al. Rosiglitazone decreases fasting plasma peptide YY3–36 in type 2 diabetic women: a possible role in weight gain?. Acta Diabetol 49 (Suppl 1), 115–122 (2012). https://doi.org/10.1007/s00592-011-0352-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-011-0352-3

Keywords

Search

Navigation