Summary
A xanthine derivative, named BL-191, was administered iv in 8 healthy volunteers alone and in association with glucose (0.33 g/kg body weight iv) or glybenclamide (1 mg iv). BL-191 was infused iv at a constant rate in a dose of 200 mg during 45 minutes. Blood glucose, free fatty acids and immunoreactive insulin were measured during one hour. It was impossible to demonstrate neither a direct effect nor an enhancement of insulin secretion during drug administration; in another experiment (treatment F) a higher dosage of BL-191 (100 mg as a priming dose + 200 mg as infusion dose) was likely ineffective. It appears that some difference in insulin response may be present in the single subject (not evident in the mean), indicating a difference in the β-cell cAMP-system sensitivity in individuals. These negative results allow some considerations on the importance of the β-cell cAMP-system in healthy human beings.
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References
Burr, I.M., Stauffacher, W., Balant, L., Renold, A.E., Grodsky, G.M.: Regulation of insulin release in perfused pancreatic tissue. Acta diabet. lat.6 (suppl. 1), 580 (1969)
Burr, I.M., Blant, L., Stauffacher, W., Renold, A.E.: Perfusion of rat pancreatic tissue in vitro: substrate modification of the ophylline-induced biphasic insulin release. J. clin. Invest.49, 2097 (1970)
Butcher, R.W., Sutherland, E.W.: Adenosine-3′5′-phosphate in biological materials. I. Purification and properties of cyclic 3′5′ nucleotide phophodiesterase and use of this enzyme to characterize adenosine −3′′ phosphate in human urine. J. biol. Chem.237, 1244 (1962)
Cerasi, E., Luft, R.: The effect of an adenosine-3′5′-monophosphate diesterase inhibitor (aminophylline) on the insulin respose to glucose infusion in prediabetic and diabetic subjects. Horm. Metab. Res.1, 162 (1969)
Hinze, H.J.: Zur Pharmakokinetik von 3,7-Dimethyl-1-(5-oxo-hexyl)-xanthin (BL 191) am Menschen. Arzneimittel-Forsch. (Drug Res.)22, 1492 (1972)
Lambert, A.E., Jeanrenaud, E.B., Renold, A.E.: Enhancement by caffeine of glucagon-induced and tolbutamide-induced insulin release from isolated fetal pancreatic tissue. Lancet1967 I, 819
Malaisse, W.J., Malaisse-Lagae, F., Mayhew, D.: A possible role for the adenylcyclase system in insulin secretion. J. clin. Invest.46, 1724 (1967)
Montague, W., Cook, J.R.: The role of adenosine 3′,5′-cyclic monophosphate in the regulation of insulin release by isolated rat islet of Langerhans. Biochem. J.122, 115 (1971)
Sutherland E.W., Butcher, R.W., Robinson, G.A., Hardman, J.G.: The role of adenosine 3′,5′-monophosphate in hormone action. In: Wirkungsmechanismen der Hormone (ed. P. Karlson) pp. 1–32. Berlin: Springer Verlag 1967
Sutherland, E.W.: The role of cyclic AMP in the control of carbohydrate metabolism. Diabetes18, 797 (1969)
Turtle, J.R., Littleton, G.C., Kipnis, D.M.: Stimulation of insulin secretion by theophylline. Nature (Lond.)213, 727 (1967)
Raptis, S., Pfeiffer, E.F.: Progress in oral therapy of diabetes mellitus with sulphonylureas of the second generation. Acta diabetol. lat.9, 965 (1972)
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Lenti, G., Pagano, G., Angotzi, G. et al. Effects of a xanthine derivative (BL 191) on insulin secretion in normal man. Eur J Clin Pharmacol 9, 189–192 (1975). https://doi.org/10.1007/BF00614016
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DOI: https://doi.org/10.1007/BF00614016