Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1 diabetes.

Abstract:

:This article examines the role of the autonomic nervous system in mediating the increase of glucagon secretion observed during insulin-induced hypoglycemia (IIH). In the first section, we briefly review the importance of the alpha-cell response in recovery from hypoglycemia under both physiologic conditions and pathophysiologic conditions, such as type 1 diabetes. We outline three possible mechanisms that may contribute to increased glucagon secretion during hypoglycemia but emphasize autonomic mediation. In the second section, we review the critical experimental data in animals, nonhuman primates, and humans suggesting that, in the absence of diabetes, the majority of the glucagon response to IIH is mediated by redundant autonomic stimulation of the islet alpha-cell. Because the glucagon response to hypoglycemia is often impaired in patients with type 1 diabetes, in the third section, we examine the possibility that autonomic impairment contributes to the impairment of the glucagon response in these patients. We review two different types of autonomic impairment. The first is a slow-onset and progressive neuropathy that worsens with duration of diabetes, and the second is a rapid-onset, but reversible, autonomic dysfunction that is acutely induced by antecedent hypoglycemia. We propose that both types of autonomic dysfunction can contribute to the impaired glucagon responses in patients with type 1 diabetes. In the fourth section, we relate restoration of these glucagon responses to restoration of the autonomic responses to hypoglycemia. Finally, in the fifth section, we summarize the concepts underlying the autonomic hypothesis, the evidence for it, and the implications of the autonomic hypothesis for the treatment of type 1 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Taborsky GJ Jr,Ahrén B,Havel PJ

doi

10.2337/diabetes.47.7.995

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

995-1005

issue

7

eissn

0012-1797

issn

1939-327X

journal_volume

47

pub_type

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