Summary
Using rat pancreatic islets and the perfused rat pancreas, the effect of exogenous insulin on insulin secretion mediated by glucose, leucine, arginine, aminophylline and tolbutamide was studied. (1) In both systems the insulin releasing capacity of glucose was inhibited by exogenous insulin. In the perfused pancreas the inhibition concerned the first and the second phase of insulin release; (2) the EC50 (half-maximal inhibitory effect of insulin on glucose-induced insulin secretion) in islets was 1.2 nM (=160 µU/ml) and 2.8 nM (390 µU/ml) in perfused pancreas; (3) exogenous insulin also inhibited insulin release in response to leucine and arginine in the isolated islet system and in the perfused pancreas; (4) using aminophylline and tolbutamide in combination with glucose, the extent of the inhibitory effect of insulin was in the range of the inhibitory effect when glucose was used alone as stimulator in islets. Data suggest that the insulinogenic action of physiological stimulators including glucose, leucine and arginine is inhibited by exogenous insulin whereas this seems not to be the case when insulin release was stimulated by aminophylline and tolbutamide. Comparing the EC50s, isolated islets seem to be more sensitive to inhibition than the perfused pancreas when glucose was used as stimulator. As far as glucose is concerned the inhibitory effect seems to depend on the extent of its concentration and/or the extent to which the mechanism of insulin release is sensitive to stimulation. The EC50 of the inhibitory effect of exogenous insulin was in the range of dissociation constant of binding of insulin to insulin receptors of islets.
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Akhtar M. S., Verspohl E., Hegner D., Ammon H. P. T.: 6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin — Diabetes26, 857, 1977.
Ammon H. P. T., Hoppe E., Akhtar M. S., Niklas H.: Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released — Interactionin vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate — Diabetes28, 593, 1979.
Ammon H. P. T., Verspohl E.: Pyridine nucleotides in pancreatic islets during inhibition of insulin release by exogenous insulin — Endocrinology99, 1469, 1976.
Ashton W. D.: The logit-transformation. With special reference to its uses in bioassay. Griffin, London, 1972.
Beischer W., Schmid M., Kerner W., Keller L., Pfeiffer E. F.: Does insulin play a role in the regulation of its own secretion? — Hormone metab. Res.10, 168, 1978.
Burgermeister W., Enzmann F., Schone H.-H.: The isolation of insulin from the pancreas. In:Hasselblatt A., von Bruchhausen F. (Eds): Insulin, part 2. Handbook of Experimental Pharmacology, Heffter-Heubner New Series XXXII/2. Springer-Verlag, Berlin-Heidelberg-New York, 1975; p. 716.
Curry D. L., Bennett L. L., Grodsky G. M.: Dynamics of insulin secretion by the perfused rat pancreas — Endocrinology83, 572, 1968.
Forgue M.-E., Freychet P.: Insulin receptors in the heart muscle. Demonstration of specific binding sites and impairment of insulin binding in the plasma membrane of the obese hyperglycemic mouse — Diabetes24, 715, 1975.
Frerichs H., Reich U., Creutzfeldt W.: Insulinsekretionin vitro: I. Hemmung der glukose-induzierten Insulinabgabe durch Insulin — Klin. Wschr.43, 136, 1965.
Goldfine I. D., Smith G. J., Wong K. Y., Jones A. L.: Cellular uptake and nuclear binding of insulin in human cultured lymphocytes: evidence for potential intracellular sites of insulin — Proc. nat. Acad. Sci. (Wash.)74, 1368, 1977.
Green I. C., Taylor K. W.: Effects of pregnancy in the rat on the size and insulin secretory response of the islet of Langerhans — J. Endocr.54, 317, 1972.
Grodsky G. M., Curry D. L., Bennett L. L., Rodrigo J. J.: Factors influencing different rates of insulin releasein vitro. In:Levine R., Pfeiffer E. F. (Eds): Mechanism and regulation of insulin secretion. II Capri Conference. Casa Ed. ‘Il Ponte’, Milano, 1968; Acta diabet. lat. 5 (Suppl. 1), 140, 1968.
Hahn H. J., Menzel R., Gottschling H. D., Jahr D.: Enhancement of glucose-stimulated insulin secretion from isolated rat pancreatic islets by human insulin antibodies — Acta endocr. (Kbh.)83, 123, 1976.
Hahn H. J., Michael R.: Untersuchüngen an Langerhansschen Inselnin vitro. V. Die Hemmung der glukoseinduzierten Insulinsekretion durch endogenes Insulinin vitro — Endokrinologie57, 98, 1970.
Heding L. G.: Determining of free and antibody-bound insulin in insulin-treated diabetic patients — Hormone metab. Res.1, 145, 1969.
Hellman B., Lernmark Å.: Inhibition of thein vitro secretion of insulin by an extract of pancreatic cells — Endocrinology84, 1484, 1969.
Lacy P. E., Kostianovsky M.: Method for the isolation of intact islets of Langerhans from the rat pancreas — Diabetes16, 35, 1967.
Lacy P. E., Williamson J. R.: Quantitative histochemistry of the islets of Langerhans. II. Insulin content of dissected B-cells — Diabetes11, 101, 1962.
Lee N. D., Williams R. H.: The intracellular localization of labeled thyroxine and labeled insulin in mammalian liver — Endocrinology54, 5, 1954.
Logothetopoulos J., Davidson J. K., Haist R. E., Best C. H.: Degranulation of beta cells and loss of pancreatic insulin after infusion of insulin antibody or glucose — Diabetes14, 493, 1965.
Loubatières A., Mariani M. M., Chapal J.: Inhibition de la sécrétion d’insuline par l’elévation de la teneur en insuline du milieu irriguant le cellules bèta des ilòts de Langerhans du pancréas — C.R. Acad. Sci. (Paris)266, 2245, 1968.
Malaisse W. J., Malaisse-Lagae F., Wright P. H.: Insulin secretionin vitro by islets from insulin-deficient rats — Proc. Soc. exp. Biol. (N.Y.)126, 474, 1967.
Sando H., Kanazawa Y., Kuzuya T.: Effect of bonito insulin on endogenous insulin secretion in dogs — Amer. J. Physiol.218, 1357, 1970.
Schatz H., Pfeiffer E. F.: Does insulin inhibit its own secretion? — Diabetologia12, 417, 1976; abstract # 230.
Schlesinger J., Schechter Y., Willingham M. C., Pastan I.: Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells — Proc. nat. Acad. Sci. (Wash.)75, 2659, 1978.
Shima K., Morishita S., Sawazaki N., Tanaka R., Tarui S.: Failure of exogenous insulin to inhibit insulin secretion in man — Hormone metab. Res.9, 441, 1977.
Sodoyez J. C., Sodoyez-Goffaux F., Foà P. P.: Evidence for an insulin-induced inhibition of insulin release by isolated islets of Langerhans — Proc. Soc. exp. Biol. (N. Y.)130, 568, 1969.
Soeldner J. S., Slone D.: Critical variables in the radioimmunoassay of serum insulin using the double antibody technique — Diabetes14, 771, 1965.
Steinke J., Patel T. N., Ammon H. P. T.: Relationship between glucose and tolbutamide-induced insulin release and insulin content in single pancreatic rat islets — Metabolism21, 465, 1972.
Tanaka R., Shima K., Sawazaki N., Matsuyama T., Kumahara Y., Yanaihara N.: Failure of exogenous insulin to inhibit C-peptide release from the perfused rat pancreas — Endocr. jap.27, 343, 1980.
Toyota T., Abe K., Kudo M.: Inhibitory action of rat insulin and synthetic rat C-peptide on insulin secretion in the perfused rat pancreas — Acta diabet. lat.14, 250, 1977.
Verspohl E. J., Ammon H. P. T.: Evidence for presence of insulin receptors in rat islets of Langerhans — J. clin. Invest.65, 1230, 1980.
Verspohl E. J., Händel M., Ammon H. P. T.: Pentosephosphate shunt activity of rat pancreatic islets: its dependence on glucose concentration — Endocrinology105, 1269, 1979.
Zawalich W. S., Karl R. C., Ferrendelli J. A., Matschinsky F. M.: Factors governing glucose induced elevation of cyclic 3′5′ AMP levels in pancreatic islets — Diabetologia11, 231, 1975.
Ziegler M., Hahn H. J., Klatt D.: Influence of isolated insulin antibodies on the insulin secretion of the islets of Langerhansin vitro — Diabetologia8, 148, 1972.
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Verspohl, E.J., Händel, M., Hagenloh, I. et al. In vitro effect of exogenous insulin on insulin secretion. Studies with glucose, leucine, arginine, aminophylline and tolbutamide. Acta diabet. lat 19, 301–317 (1982). https://doi.org/10.1007/BF02629253
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DOI: https://doi.org/10.1007/BF02629253