Effects of cholecystokinin octapeptide on the exocrine pancreas in a new rat model of type 2 diabetes.
We investigated the effects of increasing concentrations of cholecystokinin octapeptide (CCK-8) on the exocrine pancreas of a new model of type 2 diabetic rats due to the partial protection exerted by nicotinamide against the beta-cytotoxic effect of streptozotocin. CCK-8, administered for 8 successive days, exerted a biphasic action on the growth of the pancreas in non-diabetic and type 2 diabetic rats; however, the latter were less sensitive to CCK-8. Similar results were obtained in vitro by measuring the uptake of 5-bromo-2'-deoxyuridine (BrdU) in cultured isolated acinar cells. This effect was completely blocked by 3S(-)(N'-2,3-dihydro-1-methyl-2-oxo5-phenyl-1H-1,4-benzo-diazepin-3-yl)-1H-indole-2-carboxamide (L 364,718; a CCK(1) receptor antagonist) but not by (3R)-3[N'-(3-methylphenyl)ureido]-1,3-dihydro-1-methyl-5-phenyl-2H1,4-benzo-diazepin-2-one (L 365,260; a CCK(2) receptor antagonist), suggesting a direct effect via CCK(1) receptors. Binding studies showed that these effects were mediated by a single class of low-affinity CCK(1) receptors in diabetic rats and two classes of CCK-8 binding sites (with high and low affinity) in non-diabetic rats. Thus, in our new type 2 diabetes model, the loss of sensitivity of the pancreas to CCK-8 could be attributed to the loss of CCK(1) receptors of high affinity.
Kuntz
Emmanuelle
E
Centre Européen d'Etude du Diabète, Faculté de Médecine, Bâtiment IV, 11 rue Humann, 67000 Strasbourg, France.
Pinget
Michel
M
Damgé
Christiane
C
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology* / Q000502:physiology
D011949:Receptors, Cholecystokinin; D012844:Sincalide