Summary
In view of controversial findings regarding the mechanism for the increased intracellular hepatic cyclic 3′:5′ adenosine monophosphate levels in diabetic rats, we studied the dose-response relationship of the adenylate cyclase to glucagon stimulation in severely diabetic and in diabetic, insulin-treated rats. An enhanced response to glucagon and an additional augmenting effect of guanosine triphosphate on hormonal stimulation of the adenylate cyclase activity were found in diabetes which were reversible with insulin treatment. The results suggest a role of the regulatory guanyl nucleotide-binding protein in diabetes leading to an increased dose response relationship of the hepatic adenylate cyclase system to glucagon.
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Jefferson SL, Exton JH, Butcher RW, Sutherland EW, Park CR (1968) Role of adenosine 3′:5′ monophosphate in the effects of insulin and anti-insulin serum on liver metabolism. J Biol Chem 243:1031–1038
Pilkis SJ, Exton JJ, Johnson RH, Park CR (1974) Effects of glucagon on cyclic AMP and carbohydrate metabolism in liver from diabetic rats. Biochem Biophys Acta 343:250–267
Exton JH, Park CR (1968) Control of gluconeogenesis in liver. J Biol Chem 243:4188–4196
Lavine RL, Voyles N, Recant L, Perrino PV (1975) The effect of fasting on tissue cyclic AMP and plasma glucagon in the obesehyperglycemic mouse. Endocrinology 91:115–120
Unger RH, Orci D (1975) The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1:14–16
Hepp KD (1972) Adenylate cyclase and insulin action. Eur J Biochem 31:266–276
Bachmann W, Harms E, Hassels B, Henninger HP, Reutter W (1977) Studies in rat liver membrane. Biochem J 166:455–463
Mitchell RH, Hawthoren JN (1965) The site of diphosphoinositol synthesis in rat liver. Biochem Biophys Res Comm 214: 335–338
Emmelot P, Bos CJ (1962) Studies on plasma membranes of rat liver. Biochim Biophys Acta 120:369–382
de Duve C, Pressman BC, Garetta R, Wattiaux R, Applemans F (1955) Glucose-6-phosphatase, isolation and preparation. Biochem J 60:604–671
Pennington F (1961) Biochemistry of dystrophic muscle mitochondrial succinate tetrazolium reductase and adenosine triphosphatase. Biochem J 80:649–754
Lowry OH, Rosebrough NG, Farr AL, Randall RJ (1951) Determination of protein with the folin reagent. J Biol Chem 193: 265–275
Schmidt F (1961) Die enzymatische Bestimmung von Glucose und Fructose nebeneinander. Klin Wschr 39:1244–1247
Unger RH, Aguillar-Parada E, Müller WA, Eisentraut AH (1970) Studies on pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest 49: 837–846
Bachmann W, Böttger J, Haslbeck M, Mehnert H (1979) Extrapancreatic action of sulphonylureas: effects of gliquidon on insulin and glucagon binding to rat liver plasma membranes. Eur J Clin Invest 9:411–415
Salomon G, Londos G, Rodbell M (1974) A highly sensitive assay of adenylate cyclase. Analyt Biochem 58:541–548
Ross EM, Gilman AJ (1980) Biochemical properties of hormone sensitive adenylate cyclase. Ann Rev Biochem 49: 533–564
Rodbell M (1980) The role of hormone receptors and GTP regulatory proteins in membrane transduction. Science 284:17–22
Farfel Z, Kaslow HR, Bourne HR (1980) A regulatory component of adenylate cyclase is located on the inner surface of human erythrocyte membrane. Biochem Biophys Res Comm 90: 1237–1241
Pfeuffer T (1977) GTP-binding proteins in membranes and the control of adenylate cyclase activity. J Biol Chem 252: 7224–7234
Kaslow HR, Johnson GL, Brother VM, Bourne HR (1980) A regulatory component of adenylate cyclase from human erythrocyte membranes. J Biol Chem 255:3736–3741
Cassel D, Levkovitz H, Selinger Z (1977) The regulatory GTPase cycle of turkey erythrocyte adenylate cyclase. J Nucl Res 3:393–404
Pike LJ, Levkovitz HJ (1980) Activation and desentization of β-adrenergic receptor coupled GTPase and adenylate cyclase of frog and turkey erythrocyte membranes. J Biol Chem 255: 6860–6867
Gill DM, Meren R (1978) ADP ribosylation of membrane proteins catalyzed by cholera toxin, basis of activation of adenylate cyclase. Proc Natl Acad Sci USA 75:3050–3054
Nielsen ThB, Lach PM, Preston MS, Kempner E, Schlegel W, Rodbell M (1981) Structure of the turkey erythrocyte adenylate cyclase system. Proc Natl Acad Sci USA 78 (2): 722–726
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Allgayer, H., Bachmann, W. & Hepp, K.D. Increased dose-response relationship of liver plasma membrane adenylate cyclase to glucagon stimulation in diabetic rats. A possible role of the guanyl nucleotide-binding regulatory protein. Diabetologia 22, 464–467 (1982). https://doi.org/10.1007/BF00282591
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DOI: https://doi.org/10.1007/BF00282591