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.