Intraislet Hyperinsulinemia Prevents the Glucagon Response to Hypoglycemia Despite an Intact Autonomic Response

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Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response.

Because absence of the glucagon response to falling plasma glucose concentrations plays a key role in the pathogenesis of iatrogenic hypoglycemia in patients with insulin-deficient diabetes and the mechanism of this defect is unknown, and given evidence in experimental animals that a decrease in intraislet insulin is a signal to increased glucagon secretion, we examined the role of endogenous i...

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Role of the decrement in intraislet insulin for the glucagon response to hypoglycemia in humans.

OBJECTIVE Animal and in vitro studies indicate that a decrease in beta-cell insulin secretion, and thus a decrease in tonic alpha-cell inhibition by intraislet insulin, may be an important factor for the increase in glucagon secretion during hypoglycemia. However, in humans this role of decreased intraislet insulin is still unclear. RESEARCH DESIGN AND METHODS We studied glucagon responses to...

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Hypoglycemia stimulates immunoreactive glucagon (IRG) secretion and increases the activity of the sympathetic nervous system. To ascertain if the augmented alpha cell activity evoked by glucopenia is mediated by the adrenergic nervous system, the glucagon response to insulin-induced hypoglycemia of five subjects with neurologically complete cervical transections resulting from trauma, thereby d...

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Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia.

In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms...

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Loss of the decrement in intraislet insulin plausibly explains loss of the glucagon response to hypoglycemia in insulin-deficient diabetes: documentation of the intraislet insulin hypothesis in humans.

The intraislet insulin hypothesis for the signaling of the glucagon secretory response to hypoglycemia states that a decrease in arterial glucose --> a decrease in beta-cell insulin secretion --> a decrease in tonic alpha-cell inhibition by insulin --> an increase in alpha-cell glucagon secretion. To test this hypothesis in humans, a hyperinsulinemic- euglycemic ( approximately 5.0 mmol/l [90 m...

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ژورنال

عنوان ژورنال: Diabetes

سال: 2002

ISSN: 0012-1797,1939-327X

DOI: 10.2337/diabetes.51.4.958