Alpha-adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus.
The impairment of glucose-potentiated insulin secretion present in non-insulin-dependent diabetes mellitus (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L-arginine. Glucose-potentiated insulin secretion was determined on separate days during alpha-, beta-, and combined alpha- plus beta-adrenergic blockade and compared with a saline control. In normal subjects, there was no effect of alpha-, beta-, or alpha- plus beta-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 +/- 0.06 microU X ml-1 X mg-1 X dl, mean +/- SE; P less than .01) was not affected by beta-blockade but increased during alpha-blockade (0.91 +/- 0.22 microU X ml-1 X mg-1 X dl; P less than .05). However, this improvement was abolished by combined alpha- plus beta-blockade (0.32 +/- 0.07 microU X ml-1 X mg-1 X dl). Plasma norepinephrine was increased above basal levels in both normal (+260 +/- 89 pg/ml) and NIDDM (+438 +/- 162 pg/ml) subjects during alpha-blockade (P less than .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism / Q000502:physiology*; D002395:Catecholamines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D001120:Arginine; D011433:Propranolol; D010646:Phentolamine