First phase of insulin secretion stimulated by glucose plus theophylline and inhibitory effect of somatostatin in genetically diabetic mice (C57BL/KsJ-mdb).
In a previous study in C57BL/KsJ mdb/mdb mice aged 4 to 12 days we observed a diminished first phase of glucose-induced insulin secretion in vitro, and alterations in the inhibitory effect of somatostatin on insulin secretion. This study explores, using perifused pancreatic slices, whether the reduced B-cell responsiveness to somatostatin in mdb/mdb mice can be overcome upon induction of a biphasic insulin release by using theophylline. Under these conditions our results show: (1) in mdb/mdb mice aged 4 to 6 days, the restoration of the first peak of insulin secretion overcomes the reduced B-cell sensitivity to somatostatin; and (2) in mdb/mdb mice aged 7 to 12 days, the addition of theophylline only causes a partial restoration of B-cell responsiveness to somatostatin, suggesting that other mechanisms could be involved in the progressive impairement of B-cell sensitivity to somatostatin inhibitory effect.
D000375:Aging; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D006580:Genetic Carrier Screening; D005947:Glucose / Q000494:pharmacology*; D006720:Homozygote; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013004:Somatostatin / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology*
D007328:Insulin; D013004:Somatostatin; D013806:Theophylline; D005947:Glucose