Biphasic insulin secretion after intravenous but not after intraportal CCK-8 infusion in rats.
The effects of physiological doses of sulfated cholecystokinin-8 (CCK-8) on insulin secretion were investigated in unrestrained unanesthetized rats. The routes of administration were intravenous or intraportal infusion. Intravenous infusion (0.33-5.0 micrograms CCK-8.kg-1.20 min-1) resulted in a biphasic response pattern consisting of a fast 1st-min rise in plasma insulin concentration and a slower second phase that lasted throughout the infusion. The first phase showed the same amplitude with all amounts of CCK-8 administered in this study, whereas the second phase exhibited dose dependency. Blood glucose levels were lowered during all infusions of CCK-8, although the second phase of insulin release was absent with the lowest dose. These results suggest a strong stimulatory effect of CCK-8 on the pancreatic beta-cells, probably by changing the set point for glucose. The described effects of intravenous administration of CCK-8 cannot be produced when the infusion is given into the portal vein. Only very high concentrations of CCK-8 (15 micrograms.kg-1.20 min-1) produced a small increase in plasma insulin levels, indicating a strong CCK-8-eliminating mechanism in the liver. These results indicate that 1) CCK-8 evokes biphasic insulin release and a concomitant drop in glucose levels, and 2) CCK-8 acting on the beta-cell in vivo is not of intestinal origin but is probably released by the pancreatic vagal branch.
Balkan
B
B
Department of Animal Physiology, University of Groningen, Netherlands.
Steffens
A B
AB
Strubbe
J H
JH
Bruggink
J E
JE
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009994:Osmolar Concentration; D011169:Portal Vein; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D001285:Atropine; D012844:Sincalide