Glucagon is paradoxically secreted at high concentrations of glucose in rat pancreas perfused with diazoxide.

To study the role of B-cells in the regulation of glucagon secretion by glucose, the rat pancreas was perfused with 0.4 mmol/l diazoxide. Perfusate glucose was 5 mmol/l of a basal concentration, and then was decreased to 1 mmol/l, or was increased to 15 mmol/l. Insulin secretion was suppressed by diazoxide below the detectable level at each glucose concentration. Glucagon secretion was increased two-fold during the glucopenic perfusion without diazoxide, but was not changed at a low glucose concentration in the presence of diazoxide. During the glucose-excessive perfusion for 15 min, glucagon secretion was lowered from 0.69 +/- 0.17 pmol at 5 mmol/l glucose to 0.36 +/- 0.10 pmol at 15 mmol/l glucose (p < 0.05) without diazoxide, whereas that was inversely increased from 0.55 +/- 0.14 at 5 mmol/l glucose to 0.85 +/- 0.13 pmol at 15 mmol/l glucose (p < 0.05) in the presence of diazoxide. These results suggest that appropriate insulin secretion is necessary for the normal responses of glucagon secretion to hypoglycemia and hyperglycemia in the non-diabetic rat pancreas.