Glucagon secretion and alpha-cell sensitivity to somatostatin in genetically diabetic mice C57BL/KsJ-mdb.

In previous studies in C57BL/KsJ mdb/mdb mice, we observed alterations in glucose-induced insulin secretion in vitro, and a defective inhibitory effect of somatostatin on insulin secretion. In this work we studied glucagon secretion patterns under arginine-glucose stimulation, in perifused pancreatic slices from genetically diabetic mice aged 20 to 90 days. We also explored whether alpha-cells present a diminished sensitivity to somatostatin. Results showed that: a) in mdb/mdb mice aged 20 to 90 days, glucagon secretion patterns exhibited basal hypersecretion and a diminished first peak; b) somatostatin inhibited stimulated-glucagon secretion below baseline values in mdb/mdb mice aged 20 to 30 days. In later stages (40 to 90 days), somatostatin exerted a lower inhibitory effect since glucagon levels remain above basal values. This could indicate a progressive impairment in alpha-cell sensitivity to somatostatin, as it was previously observed in beta-cells.