Summary
The effects of two different cholecystokinin variants, CCK-39 and the carboxyl-terminal octapeptide CCK-8, on basal and stimulated insulin secretion were studied in the mouse. It was found that both peptides had a dose-dependent stimulating action on insulin secretion with a maximal response of similar magnitude at a dose level of about 5 nmol/kg body weight. This dose induced an increase of plasma concentrations of immunoreactive insulin of about 100 μU/ml. The calculated half-maximal dose was 2.12 nmol/kg for CCK-39 and 3.18 nmol/kg for CCK-8. The insulin-secretory response to CCK-39 and CCK-8 in the absence of other secretagogues was partially abolished by pretreatment with the cholinergic blocker methylatropine as well as with the β-adrenoceptor blocker L-propranolol. Thus, this great insulin-secretory response to the two peptides seemed to be dependent on intact muscarinic and β-adrenergic receptors. CCK-39 or CCK-8 administered in a threshold dose prior to half-maximal doses of D-glucose, the cholinergic agonist carbachol, or the β-adrenergic agonist L-isopropylnoradrenaline (L-IPNA), respectively, displayed different influences on insulin release. CCK-39 potentiated glucose- as well as carbachol-induced insulin secretion, whereas it did not influence L-IPNA-induced insulin release. An equimolar dose of CCK-8, on the contrary, had no apparent effect on either glucose-, carbachol-, or L-IPNA-induced insulin release. This observation indicates that stimulated insulin release is influenced by amino acid sequences other than those of the C-terminal octapeptide in CCK-39 and that the response of the stimulated insulin-secreting cells to CCK-39 is dependent on the nature of the secretagogue.
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Ahrén, B., Lundquist, I. Effects of two cholecystokinin variants, CCK-39 and CCK-8, on basal and stimulated insulin secretion. Acta diabet. lat 18, 345–356 (1981). https://doi.org/10.1007/BF02042819
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DOI: https://doi.org/10.1007/BF02042819