Pathophysiology of insulin secretion in diabetes mellitus.
In normal man, glucose serves to regulate basal insulin secretion by its participation with insulin in a feedback loop. In addition, glucose stimulates insulin secretion directly and potentiates insulin responses to nonglucose stimuli such as amino acids, beta-adrenergic stimuli, and gut hormones. Maximal glycemic potentiation of the acute insulin response to IV arginine occurs at a glucose level of approx. 450 mg/dl. In patients with noninsulin dependent diabetes mellitus (NIDDM), basal insulin levels have usually been reported as normal, but if plasma glucose is lowered to normal levels, a deficiency of basal insulin becomes apparent. In addition, the first phase (0-10 min) insulin response to IV glucose is absent in virtually all patients with overt NIDDM. In contrast, the second-phase (greater than 10 min) response is often preserved in NIDDM due to its maintenance by ambient hyperglycemia. Similarly, insulin responses to nonglucose stimuli such as arginine often appear normal in NIDDM because of potentiation by hyperglycemia. However, insulin responses to arginine are lower than those of nondiabetic controls when compared at multiple matched glucose levels. Indeed, maximal potentiation by glucose of the insulin response to arginine is markedly subnormal in NIDDM, suggesting a loss of functional B cell secretory capacity. In patients with long-standing insulin-dependent diabetes mellitus (IDDM), basal insulin secretion and insulin responses to all stimuli are virtually absent. However, in a remission phase, or in IDDM of short duration, basal insulin secretion and insulin responses to nonglucose stimuli may be relatively preserved. Therefore, islet dysfunction in IDDM and NIDDM, while etiologically different, share some common pathophysiological features.
D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine