Summary
The rat epididymal fat tissue was incubated with glucose differently labelled with 14C, and the effect of palmitate bound to albumin was studied in the absence or presence of insulin. No inhibition by palmitate of the glucose metabolism was observed. On the contrary, it was demonstrated that palmitate stimulates the different pathways of the glucose metabolism, particularly the fatty acid neosynthesis. The results are discussed in relation to the glucose and palmitate metabolism in the adipose cell, and in relation to the role in vivo of the adipose tissue in the decrease of the glucose assimilation observed in conditions which abnormally increase the serum level of free fatty acids.
Résumé
Le tissu adipeux épididymaire du rat a été incubé avec du glucose différemment marqué au 14O et l'effet du palmitate lié à l'albumine a été étudié en l'absence et en présence d'insuline. Aucune inhibition, par le palmitate, du métabolisme du glucose n'a été observée; au contraire, il a été démontré que le palmitate stimule les différentes voies du métabolisme du glucose, en particulier la néosynthèse des acides gras. Les résultats sont discutés en fonction du métabolisme du glucose et du palmitate dans la cellule adipeuse, et en fonction du rôle tenu in vivo par le tissu adipeux dans la diminution de l'assimilation du glucose observée dans des conditions qui élèvent anormalement le taux des acides gras libres sériques.
Zusammenfassung
Das epididymale Fettgewebe der Ratte wurde mit verschieden markierter 14C-Glucose inkubiert, und der Effekt von mit Eiweiß gebundenem Palmitat in Ab- und Anwesenheit von Insulin untersucht. Es wurde keine Hemmung des Glucosemetabolismus durch Palmitat beobachtet; hingegen wurde erwiesen, daß Palmitat die verschiedenen Wege des Glucosemetabolismus anregt, besonders die Neosynthese der Fettsäuren. Die Resultate werden wie folgt diskutiert: 1. im Hinblick auf den Metabolismus von Glucose und Palmitat in der Fettzelle, 2. im Hinblick auf die in vivo-Rolle des Fettgewebes bei der Verminderung der Glucoseassimilierung. Diese Verringerung wurde unter Bedingungen beobachtet, die den Serumspiegel der freien Fettsäuren ungewöhnlich stark erhöhen.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Andres, R., and K.L. Zierler: Spontaneous and insulin induced resistance of peripheral tissues to insulin in diabetes. Clin. Res. 6, 250–259 (1958).
Ball, E.G., and R.L. Jungas: Some effects of hormones on the metabolism of adipose tissue. Recent Progr. Hormone Res. 20, 183–214 (1964).
—: Studies on the metabolism of adipose tissue. XIII. The effect of anaerobic conditions and dietary regime on the response to insulin and epinephrine. Biochemistry 2, 586–582 (1963).
Bally, P.B., H. Kappeler, E.R. Froesch, and A. Labhart: Effects of glucose on spontaneous limitation of lipolysis in isolated adipose tissue. A potential regulatory mechanism. Ann. N.Y. Acad. Sci. 131, 143–156 (1965).
Bally, P.R., G.F. Cahill, Jr., B. Leboeuf, and A.E. Renold: Studies on rat adipose tissue in vitro. V. Effects of glucose and insulin on the metabolism of palmitate-1-14C. J. biol. Chem. 235, 333–336 (1960).
Bierman, E.L., V.P. Dole, and T.N. Roberts: An abnormality of nonesterified fatty acids metabolism in diabetes mellitus. Diabetes 6, 475–479 (1957).
Bray, G.A.: A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter. An. Biochem. 1, 279–285 (1960).
Bortz, W., and F. Lynen: The inhibition of acetyl-CoA carboxylate by long chain acyl-CoA derivatives. Biochem. Z. 337, 505–509 (1963).
Bowman, B.H.: Effect of diabetes, fatty acids and ketone bodies on tricarboxylic acid cycle metabolism in the perfused rat heart. J. biol. Chem. 241, 3041–3048 (1966).
Cahill, G.F., Jr., B. Leboeuf, and R.B. Flinn: Studies on rat adipose tissue in vitro. VI. Effect of epinephrine on glucose metabolism J. biol. Chem. 235, 1246–1250 (1960).
Delisle, G., and I.B. Fritz: Interrelations between hepatic fatty acid oxidation and gluconeogenesis: a possible regulatory role of carnitine palmityl-transferate. Proc. nat. Acad. Sci. (Wash.) 58, 790–797 (1967).
Denton, M., R.E. Yorke, and P.J. Randle: Measurements of concentrations of metabolites in adipose tissue and effects of insulin, alloxan-diabetes and adrenaline. Biochem. J. 100, 407–419 (1966).
Denton, R.M., and P.J. Randle: Citrate and the regulation of adipose tissue phosphofructokinase. Biochem. J. 100, 420–423 (1966).
Dole, V.P.: Relation between non-esterified fatty acids in plasma and the metabolism of glucose. J. clin. Invest. 35, 150–154 (1956).
— The fatty acid pool in adipose tissue. J. biol. Chem. 236, 3121–3124 (1961).
—, and H. Meinertz: Microdetermination of long-chain fatty acids in plasma and tissues. J. biol. Chem. 235, 2595–2599 (1960).
Exton, J.H., and C.R. Park: Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats. J. biol. Chem. 242, 2622–2636 (1967).
Felber, J.-P., and A. Vannotti: Effects of fat infusion on glucose tolerance and insulin plasma levels. Med. Exp. 10, 153–156 (1964).
—, et A. Vannotti: Décompensation pancréatique et diabète. Rev. franç. Endocr. Clin. 7, 211–226 (1966).
—, N. Zabagoza, L. Grassi, A.J. Moody et A. Vannotti: Utilisation diminuée du glucose et accumulation de graisse chez l'obèse diabétique. Schweiz. med. Wschr. 96/47, 1575–1578 (1966).
Flatt, J.-P., and E.G. Ball: Studies on the metabolism of adipose tissue. XV. An evaluation of the major pathways of glucose catabolism as influenced by insulin and epinephrine. J. biol. Chem. 239, 675–685 (1964).
Freinkel, N.: Extrathyroidal actions of pituitary thyrotropin: effects on the carbohydrate, lipid and respiratory metabolism of rat adipose tissue. J. clin. Invest. 40, 476–489 (1961).
Friedmann, B., E.H. Goodman, and S. Weinhouse: Effect of insulin and fatty acids on gluconeogenesis in the rat. J. biol. Chem. 242, 3620–3627 (1967).
Froesh, E.R., H. Bürgi, E.B. Ramseier, and A. Labhart: Antibody suppressible and non-suppressible insulin-like activities in human serum and their physiological significance. An insulin assay with adipose tissue of increased precicion and specificity. J. clin. Invest. 42, 1816–1834 (1963).
Garland, P.B., E.A. Newsholme, and P.J. Randle: Regulation of glucose uptake by muscle. 9. Effect of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate/pyruvate and L-glycerol 3 phosphate/dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem. J. 93, 665–678 (1964).
—, and P.J. Randle: Regulation of glucose uptake by muscle. 10. Effect of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty-acyl-coenzyme A, glycerol phosphate and citrate-cycle, intermediates in rat heart and diaphragm muscles. Biochem. J. 93, 678–687 (1968).
Gjedde, F.: Studies of the ILA of Serum. III. Influence of the Pancreas on the ILA of Serum. Acta endocr. (Kbh.) 57, 505–528 (1964).
Goodman, D.S.: The interaction of human serum albumin with long-chain fatty acid anions. J. Amer. chem. Soc. 80, 3892–3898 (1958).
Gromova, K.G.: Vop. med. Him. 6, 631–639 (1964).
Hales, C.N., and P.J. Randle: Effect of low carbohydrate diet and diabetes mellitus on plasma concentrations of glucose, non-esterified fatty acids and insulin during oral glucose tolerance test. Lancet 1963 I, 790–794.
Ikkos, D., R. Luft, C.-A. Gemzell, and S. Almovist: Effect of human growth hormone on glucose tolerance and some intermediary metabolites in man. Studies in healthy subjects given human growth hormone and in patients with acromegaly. Acta endocr. (Kbh.) 39, 547–566 (1962).
Il'in, V.S.: The mechanism of action of insulin: primary and secondary metabolic disturbances in experimental diabetes. Fed. Proc. 25, T 1034–1040 (1966).
Jeanbenaud, B., and A.E. Renold: Studies on rat adipose tissue in vitro. VII. Effects of adrenal cortical hormones. J. biol. Chem. 235, 2217–2223 (1960).
Jungas, R.L., and E.G. Ball: Studies on the metabolism of adipose tissue. V. The effect of a growth hormone preparation and insulin on the oxygen consumption, glucose uptake, and lactic acid production. J. biol. Chem. 235, 1894–1899 (1960).
—: Studies on the metabolism of adipose tissue. XII. The effects of insulin and epinephrine on FFA and glycerol production in the presence or absence of glucose. Biochemistry 2, 383–388 (1963).
Katz, J., B.R. Landau, and G.E. Bartsch: The pentose cycle, triosephosphate isomerization, and lipogenesis in rat adipose tissue. J. biol. Chem. 241, 727–738 (1966).
Korchak, H.M., and E.J. Masoro: Free fatty acids as lipogenic inhibitors. Biochim. biophys. Acta 84, 750–753 (1964).
Kerpel, S., E. Shafrir, and B. Shapiro: Mechanism of fatty acid assimilation in adipose tissue. Biochem. biophys. Acta 46, 495–504 (1961).
Kessler, J.I., M. Demeny, and H. Sobotka: Rates of tissue uptake of palmitic-1-14C complexed with albumin by two different procedures. J. Lip. Res. 8, 185–190 (1967).
Leboeuf, B., and G.F. Cahill: The regulation of fatty acid synthesis and direct oxidative pathway in adipose tissue. Fed. Proc. 19, 226 (1960).
Studies on rat adipose tissue in vitro. VIII. Effect of preparations of pituitary adreno-corticotropic and growth hormone on glucose metabolism. J. biol. Chem. 236, 41–46 (1961).
Leites, S.M., and N.K. Davtyan: Influence of glucose uptake by adipose tissue on its lipolytic activity during action of certain hormones and in experimental diabetes. Fed. Proc. 25, T 1009 (1966).
Leveille, G.: Control of lipogenesis in adipose tissue of fasted and fed meal-eating rats. J. Nutr. 92, 460–466 (1967).
—: Lipogenesis in adipose tissue of meal-fed rats. A possible regulatory role of α-glycerophosphate formation. Canad. J. Physiol. Pharmacol 45, 201–213 (1967).
Lundbaeck, K.: Metabolic abnormalities in starvation diabetes. Yale J. Biol. Med. 20, 553–562 (1948).
Martin, D.B., and P.R. Vageloos: The mechanism of tricarboxylic acid cycle regulation of fatty acid synthesis. J. biol. Chem. 237, 1787–1792 (1962).
Masord, E.J.: Mechanisms related to the homeostatic regulation of lipogenesis. Ann. N.Y. Acad. Sci. 131, 199–205 (1965).
Matsuhashi, M., S. Matsuhashi u. F. Lynen: Zur Biosynthese der Fettsäuren. V. Die Acetyl-CoA carboxylase aus Rattenleber und ihre Aktivierung durch Citronensäure. Biochem. Z. 340, 263–289 (1964).
McLean, P., J. Brown, E. Walters, and Greensladek: Effect of alloxan diabetes on multiple forms of hexokinases in adipose tissue and lung. Biochem. J. 105, 1301–1305 (1967).
Nestel, P.D., K.F. Carrill, and M.S. Silverstein: Influence of free fatty acids metabolism on glucose tolerance. Lancet 1964 II, 115–117.
Newsholme, E.A., and P.J. Randle: Regulation of glucose uptake by muscle. 7. Effect of fatty acids, ketone bodies and pyruvate, and of alloxan diabetes, starvation, hypophysectomy and adrenalectomy, on the concentration of hexose phosphates, nucleotides and inorganic phosphate in perfused rat heart. Biochem. J. 93, 641–651 (1964).
Pogson, C.I., and R.M. Denton: Effect of alloxan diabetes, starvation and refeeding on glycolytic-kinase activities in rat epididymal adipose tissue. Nature (Lond.) 216, 156–157 (1967).
Raben, M.S., and C.H. Hollenberg: Effect of growth hormone on plasma fatty acids. J. clin. Invest. 38, 484–488 (1959).
Randle, P.J., E.A. Newsholme, and P.B. Garland: Regulation of glucose uptake by muscle. 8. Effect of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem. J. 93, 652–665 (1964).
—, and E.A. Newsholme: The glucose-fatty acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963 I, 785–789.
—, and C.N. Hales: The glucose fatty acid cycle in obesity and maturity onset diabetes mellitus. Ann. N.Y. Acad. Sci. 131, 324–333 (1965).
Rodbell, M.: Metabolism of isolated fat cells. I. Effect of hormones on glucose metabolism and lipolysis. J. biol. Chem. 239, 375–380 (1964).
Rubinstein, D., A.M. Daniel, S. Chiu, and J.-P. Beck: The effect of homogeneization on free and esterified fatty acid pools in adipose tissue. Canad. J. Biochemistry 43, 271–280 (1965).
Schalch, D.S., and D.M. Kipnis: Abnormalities in carbohydrate tolerance associated with elevated plasma non-esterified fatty acids. J. clin. Invest. 44, 2010–2020 (1965).
Shapiro, B., I. Chowers, and G. Rose: Fatty acid uptake and esterification in adipose tissue. Biochim. biophys. Acta 23, 115–125 (1957).
Shipp, J.C.: Interrelation between carbohydrate and fatty acid metabolism of isolated perfused rat heart. Metabolism 13, 852 (1954).
Silperstein, M.: In: Diabetes Moscow 90 (1964).
Stein, M.F., D.M. Kipnis, and W.H. Daughaday: The effect of human growth hormone on plasma insulin dynamics in man. J. Lab. clin. Med. 60, 1022 (1962).
Seyfert, W.A., and L.L. Madison: Physiologic effects of metabolic fuels on carbohydrate metabolism. Diabetes 16, 765–776 (1967).
Teufel, H., L.A. Menahan, J.C. Shipp, S. Böning, and O. Wieland: Effect of oleic acid on the oxidation and gluconeogenesis from (1-14C) pyruvate in the perfused rat liver. Europ. J. Biochemistry 2, 182–186 (1967).
Vaughan, M.: The metabolism of adipose tissue in vitro. J. Lip. Res. 2, 293–316 (1961).
Verner, J.V., W.G. Blackard, and F. Engel: Some factors modifying the actions of hormones on glucose uptake by adipose tissue in vitro. Endocrinology 70, 420–428 (1962).
Weber, G., H.J.H. Convery, M.A. Lea, and N.B. Stamm: Feedback inhibition of key glycolytic enzymes in liver: action of free fatty acids. Science 154, 1357–1360 (1966).
Winand, J., J. Furnelle et J. Christophe: Métabolisme in vitro du tissu adipeux. V. Hétérogénéité et sub-hétérogénéité du pool des NEFA dans le tissu adipeux épididymaire de la souris normale. Effets in vitro du glucose, de l'adrénaline et de l'insuline. Bull. Soc. Chim. biol. (Paris) 49, 1331–1356 (1967).
Winegrad, A.E.: Adipose tissue in diabetes. Handbook of Physiology Section 5. Adipose tissue (A.E. Renold and G.F. Cahill Jr. eds.) chap. 32, pp. 319–329 (1965).
Winegrad, A.I., and A.E. Renold: Studies on rat adipose tissue in vitro. I. Effect of insulin on the metabolism of glucose, pyruvate and acetate. J. biol. Chem. 233, 267–272 (1958).
Young, J.W., E. Shrago, and H.A. Lardy: Metabolic control of enzymes involved in lipogenesis and gluconeogenesis. Biochemistry 3, 1687–1692 (1964).
Author information
Authors and Affiliations
Additional information
This work was supported by a grant of the “Fonds National Suisse de la Recherche Scientifique” (request No. 4325).
We should like to thank Miss M. Plattenburg for her technical assistance.
Rights and permissions
About this article
Cite this article
Zaragoza, N., Felber, J.P. Study of the metabolism in vitro of glucose in the rat epididymal fat tissue. Diabetologia 5, 284–292 (1969). https://doi.org/10.1007/BF00452900
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00452900