The influence of cultivation on (pro-)insulin biosynthesis and secretion of isolated pancreatic islets of C57BL-mice, long-term treated with glibenclamide in vivo.

Long-term treatment of C57Bl/KsJ and C57Bl/6J mice with glibenclamide in vivo caused a diminished response of insulin to high glucose concentrations (20 mmol/l). Islets of those mice were investigated to answer the question whether it is possible to overcome this diminution of glucose sensitivity by cultivation in presence of high glucose (20 mmol/l). The insulin release of islets of glibenclamide treated mice was significantly lowered also in the first 48 h of cultivation. In the following short-term incubation (2 h) no differences in the glucose stimulated insulin secretion could be seen. The second cultivation period (48-96 h) confirmed these results. Both groups of islets (controls and glibenclamide treated) reached comparable values in insulin release. Cultivation of islets of glibenclamide treated mice in presence of 20 mmol/l glucose for at least 2 days led to a restoration of the glucose sensitivity of insulin release. Insulin biosynthesis, judged by measuring 3H-leucine incorporation into (pro-)insulin, was largely unaffected. In all experimental conditions the insulin content was comparable to that of controls.