Regulation of glucose uptake by muscle. 5. Effects of anoxia, insulin, adrenalin and prolonged starving on concentrations of hexose phosphates in isolated rat diaphragms and perfused isolated rat heart.
Since diazoxide causes hyperglycemia and since it has been demonstrated that tolbutamide and chlorpropamide are capable of reversing this hyperglycemia (Kvam and Stanton 1964, Tabachnick, Culbenkian and Seidman 1964), it appears probable that the large increase in insulin secretion seen with tolbutamide and chlorpropamide in these animaIs results from a necessity to overcome diazoxide-induced glucose elevations. Loubatieres has suggested that there is an antagonism between the eff~cts of sulfonylurea hypoglycemic agents and diazoxide on insulin secretion at a cellular level in the ß-cell of the pancreas (Loubatieres, Mariani, Alric, Chapal and Portal 1967). Thus, the large insulin increases seen in mice receiving the combination of diazoxide pretreatment followed by a sulfonylurea could be a reflection of inhibition of insulin release resulting in a buildup of available insulin in the pancreas. The reversal of this inhibition by tl;le sulfonylurea, plus the stimulation by the high circulating glucose concentration results in an exaggerated insulin release. This hypo thesis is supported by the morphologicaI studies of Creutzfeldt. Creutzfeldt. Frerichs, Pering, and Sicklinger (l969), and Yoshinaga (1969).
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