Reversal of defective glucagon responses to hypoglycemia in insulin-dependent autoimmune diabetic BB rats.

Abstract:

:The intraislet insulin hypothesis has been proposed to explain absent glucagon responses to hypoglycemia. Recently we directly confirmed this hypothesis by restoring glucagon secretion via provision of a pancreatic artery insulin infusion, which was switched off at the time of hypoglycemia in Wistar rats made diabetic by streptozotocin. The current study examined this hypothesis in a model of spontaneous, autoimmune diabetes, the insulin-dependent diabetic BB rat. The insulin switch-off signal restored the defective glucagon responses to hypoglycemia. However, the magnitude of the restored response was markedly less than that observed in control nondiabetic BB rats (4- to 5-month-old diabetic BB rats = 147 +/- 27; 2-month-old nondiabetic BB rats = 1038 +/- 112 pg/ml, peak delta; P < 0.0001). Because time was required for the BB rat to spontaneously develop diabetes, we asked whether the incomplete restoration of the glucagon response might be related to the animals' growth and development. This led us to compare the glucagon response to hypoglycemia in nondiabetic BB and Wistar rats at 2 and 4-5 months of age. We observed age-related deterioration of not only glucose tolerance and insulin sensitivity but also glucagon responses to hypoglycemia in both strains. There was no significant difference between the glucagon responses to hypoglycemia in age-matched nondiabetic BB rats and diabetic BB rats provided with the insulin switch-off signal. We conclude that defective glucagon responses to hypoglycemia in BB rats can be corrected by restoring regulation of alpha-cell function by insulin.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Zhou H,Zhang T,Oseid E,Harmon J,Tonooka N,Robertson RP

doi

10.1210/en.2006-1375

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

2863-9

issue

6

eissn

0013-7227

issn

1945-7170

pii

en.2006-1375

journal_volume

148

pub_type

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