Summary
Adipose tissue from streptozotocin-diabetic rats exhibits half-maximal lipolytic responses (FFA, glycerol release, increase in tissue FFA) to epinephrine at hormone concentrations 5–10 times lower than those required for half-maximal stimulation of lipolysis in adipose tissue from normal rats. The lipolytic response to epinephrine also occurs more promptly and the antilipolytic effect of insulin in the presence of submaximal epinephrine concentrations is much less pronounced than in normal tissue. In contrast, diabetic adipose tissue is less responsive to ACTH and glucagon than normal tissue. Half-maximal lipolytic responses are elicited by similar dibutyryl cyclic AMP concentrations in both tissues. Insulin treatment of diabetic rats during 24 hrs restores the lipolytic response of their adipose tissue to epinephrine to nearly normal. Our findings point to an abnormality of diabetic adipose tissue possibly related to the hypersensitivity of catecholamines encountered in denervated organs which are adrenergically innervated. They are consistent with the present concept of different hormone discriminators on the fat cell membrane and offer a further explanation for increased FFA mobilization in the diabetic state.
Article PDF
Similar content being viewed by others
References
Havel, R. J.: Autonomic nervous system and adipose tissue. In: Handbook of Physiology, Section V. Adipose tissue (eds. A. E. Renold, G. F. Cahill, Jr.), p. 577. Washington D. C. 1965
Winegrad, A. I.: Adipose tissue in diabetes. In: Handbook of Physiology, Section V. Adipose tissue (eds. A. E. Renold, G. F. Cahill, Jr.), pp. 324–328. Washington D. C. 1965
Biermann, E.L., Dole, V.P., Roberts, T.N.: An abnormality of nonesterified fatty acid metabolism in diabetes mellitus. Diabetes6, 475–479 (1957)
Dole, V.P.: Fat metabolism in diabetes. Bull. N. Y. Acad. Med.34, 21–25 (1958)
Vaughan, M.: The metabolism of adipose tissue in vitro. J. Lipid Res.2, 293–316 (1961)
Rizack, M.A.: An epinephrine-sensitive lipolytic activity in adipose tissue. J. biol. Chem.236, 657–662 (1961)
Wieland, O., Suyter, M.: Glycerokinase. Isolierung und Eigenschaften des Enzymes. Biochem. Z.329, 320–331 (1957)
Shapiro, B., Chowers, I., Rose, G.: Fatty acid uptake and esterification in adipose tissue. Biochim. biophys. Acta (Amst.)23, 115–120 (1957)
Froesch, E. R.: Fructose metabolism in adipose tissue from normal and diabetic rats. In: Handbook of Physiology, Section V. Adipose tissue (eds. A. E. Renold, G. F. Cahill, Jr.), pp. 281–293. Washinton D. C. 1965
Meyer, U.A., Sturzenegger, V., Froesch, E.R.: Transport and metabolism of glucose, insulin sensitivity and lipolysis of epididymal adipose tissue of alloxan-diabetic rats after prolonged incubation in vitro. Diabetologia4, 87–94 (1968)
Froesch, E.R., Bürgi, H., Ramseier, E.B., Bally, P., Labhart, A.: Antibody-suppressible and nonsuppressible insulin-like activities in human serum and their physiologic significance. An insulin assay with adipose tissue of increased precision and specificity. J. clin. Invest.42, 1816–1834 (1963)
Duncombe, W.G.: The colorimetric microdetermination of longchain fatty acids. Biochem. J.88, 7–10 (1963)
Angel, A., Desai, K.S., Halperin, M.L.: Intracellular accumulation of free fatty acids in isolated white adipose cells. J. Lipid Res.12, 104–111 (1971)
Eggstein, M., Kreutz, F.H.: Eine neue Bestimmung der Neutralfette im Blutserum und Gewebe. Klin. Wschr.44, 262–267 (1966)
Jungas, R.L., Ball, E.G.: Studies on the metabolism of adipose tissue. XII. The effects of insulin and epinephrine on free fatty acid and glycerol production in the presence and absence of glucose. Biochemistry2, 383–388 (1963)
Butcher, R.W., Baird, C.E., Sutherland, E.W.: Effects of lipolytic and antilipolytic substances on adenosine 3′5′-monophosphate levels in isolated fat cells. J. biol. Chem.243, No. 8, 1705–1712 (1968)
Braun, T., Hechter, O.: Glucocorticoid regulation of ACTH sensitivity of adenyl cyclase in rat fat cell membranes. Proc. nat. Acad. Sci. (Wash.)66, No. 3, 995–1001 (1970)
Butcher, R.W.: Cyclic 3′, 5′ AMP and the lipolytic effects of hormones in adipose tissue. Pharmacol. Rev.18, 237–241 (1966)
Butcher, R.W., Sneyd, J.G.T., Park, C.R., Sutherland, E.W.: Effect of insulin on adenosine 3′, 5′-monophosphate in the rat epididymal fat pad. J. biol. Chem.241, 1651–1653 (1966)
Butcher, R.W.: Cyclic AMP, lipolysis and antilipolysis. In: Adipose tissue, regulation and metabolic functions (eds. B. Jeanrenaud, D. Hepp), p. 6. Stuttgart: Georg Thieme Verlag, New York-London: Academic Press 1970
Kaukel, E., Mundhenk, K., Hilz, H.: N6-monobutyryladenosine 3′:5′-monophosphate as the biologically active derivative of dibutyryladenosine 3′:5′ monophosphate in HeLa 53 cells, Europ. J. Biochem.27, 197–200 (1972)
Jarett, L., Steiner, A.L., Smith, R.M., Kipnis, D.M.: The involvement of cyclic AMP in the hormonal regulation of protein synthesis in rat adipocytes. Endocrinology90, 1277–1284 (1972)
Froesch, E.R., Bürgi, H., Bally, P., Labhart, A.: Insulin inhibition of spontaneous adipose tissue lipolysis and effects upon fructose and glucose metabolism. Molec. Pharmacol.1, No. 3, 280–296 (1965)
Birnbaumer, L., Rodbell, M.: Adenyl cyclase in fat cells. II. Hormone receptors. J. biol. Chem.244. No. 13, 3477–3428 (1969)
Soderling, T.R., Corbin, J.D., Park, C.R.: Regulation of adenosine 3′, 5′-monophosphate-dependent protein kinase. II. Hormonal regulation of the adipose tissue enzyme. J. biol. Chem.248, No. 2, 1822–1829 (1973)
Huttunen, J.K., Steinberg, D.: Activation and phosphorylation of purified adipose tissue hormone-sensitive lipase by cyclic AMP-dependent protein kinase. Biochim. biophys. Acta (Amst.)239, 411–427 (1971)
Senft, G., Schultz, G., Munske, K., Hoffmann, M.: Influence of insulin on cyclic 3′, 5′-AMP phosphodiesterase activity in liver, skeletal muscle, adipose tissue and kidney. Diabetologia4, 322–329 (1968)
Trendelenburg, U.: Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev.15, 225–276 (1963)
Trendelenburg, U.: Mechanisms of supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev.18, 629–640 (1967)
Deguchi, T., Axelrod, J.: Superinduction of serotonin-N-acetyltransferase and supersensitivity of adenylcyclase to catecholamines in denervated pineal gland. Molec. Pharmacol.9, 612–618 (1973)
Rosell, S., Belfrage, E.: Adrenergic receptors in adipose tissue and their relation to adrenergic innervation. Nature253, 738–739 (1975)
Rudinger, J., Pliška, V., Krejči, I.: Oxytocin analogs in the analysis of some phases of hormone action. Rec. Progr. Horm. Res.28, 131–166 (1972)
Hertting, G.: The fate of3H-isoproterenol in the rat. Biochem. Pharmacol.13, 1119–1128 (1964)
Author information
Authors and Affiliations
Additional information
Supported by grant No. 3.7180.72 from the Swiss National Fonds. A preliminary report of part of this work has been given at the Eighth Annual Meeting of the European Society for Clinical Investigation at Rotterdam on April 25–27, 1974 and at the Tenth Annual Meeting of the European Association for the Study of Diabetes in Jerusalem on September 11–13, 1974.
Rights and permissions
About this article
Cite this article
Zapf, J., Feuerlein, D., Waldvogel, M. et al. Increased sensitivity of diabetic rat adipose tissue towards the lipolytic action of epinephrine. Diabetologia 11, 509–516 (1975). https://doi.org/10.1007/BF01222100
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01222100