Summary
Mild hyperglycemia was induced in normal rats by oral administration of both diazoxide
and D-glucose. After 48 hours of such a treatment, the insulin and glucagon secretory
responses of the perfused pancreas to α-and β-D-glucose (3.3 mM) were examined in
the presence of 10.0 mM L-leucine. The output of insulin, but not that of glucagon,
and the perfusion pressure were higher in treated than control rats. The α-anomer
of D-glucose was a more potent insulin secretagogue than β-D-glucose in both control
and treated rats. However, the α/β ratio in insulin output was twice higher in control
than treated rats. By analogy with other experimental models of diabetes, the attenuation
in the anomeric difference of glucose-stimulated insulin output in the treated rats
could reflect an altered secretory response to α- rather than β-D-glucose. These findings
suggest that hyperglycemia provokes, as a function of its severity and duration, first
attenuation and then suppression, if not inversion, of the anomeric preference f or
β-D-glucose in insulin release. They are also compatible with the hypothesis that
the anomeric malaise, associated with B-cell glucotoxicity, is caused by a progressive
accumulation of glycogen in this cell.
Key words
Diazoxide - Perfused Pancreas - D-Glucose Anomers - Insulin Secretion - Glucagon Secretion
