A temporal study of somatostatin secretion and its inhibitory effect in genetically diabetic mice (C57BL/KsJ-db/db).
Somatostatin (SRIF) acts as a physiological regulator of insulin and glucagon secretion. This study explored whether alterations in SRIF secretion and activity in perifused pancreas from spontaneously diabetic mice (C57BL/KsJ-db/db) could be correlated with hypersecretion of insulin by the beta-cells. SRIF release upon stimulation with 27.5 mM glucose was biphasic in controls, whereas a first phase peak was absent in 30-to 90-day-old diabetic mice (db/db). Twelve- to 28-day-old db/db mice showed two distinct patterns compared to controls: biphasic hypersecretion in the 12- to 20-day-old group compared to normal secretion in the 22- to 28-day-old group. Basal SRIF secretion showed a tendency to be elevated above controls in some of the db/db age groups, but the difference was not statistically significant. Insulin release from control pancreases was biphasic, whereas in db/db mice, basal hypersecretion, absence of the first peak, and second phase hypersecretion were observed. beta-Cell sensitivity to the inhibitory effect of SRIF was diminished in db/db mice aged 12-90 days. Diazoxide, on the contrary, inhibited insulin secretion from the pancreas of diabetic and normal mice to the same extent. The results suggest that altered secretion of and response to SRIF in C57BL/KsJ-db/db mice might provide an explanation for the anomalies in insulin secretion in the first stages of this type of diabetic syndrome.
D000375:Aging; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology
D007328:Insulin; D013004:Somatostatin; D005947:Glucose; D003981:Diazoxide