This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, H. Articles by Robertson, R. P. Search for Related Content PubMed PubMed Citation Articles by Zhou, H. Articles by Robertson, R. P.

Reversal of Defective Glucagon Responses to Hypoglycemia in Insulin-Dependent Autoimmune Diabetic BB Rats

Pacific Northwest Research Institute and the Division of Endocrinology (H.Z., T.Z., E.O., J.H., N.T., R.P.R.), Departments of Medicine and Pharmacology, Seattle, Washington 98122; and Departments of Pharmacology and Medicine (R.P.R.), University of Washington, Seattle, Washington 98108

Address all correspondence and requests for reprints to: R. Paul Robertson, Pacific Northwest Research Institute, 720 Broadway, Seattle, Washington 98122. E-mail: rpr{at}pnri.org.

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 -cell function by insulin.

This article has been cited by other articles:

				X. Fan, Y. Ding, S. Brown, L. Zhou, M. Shaw, M. C. Vella, H. Cheng, E. C. McNay, R. S. Sherwin, and R. J. McCrimmon Hypothalamic AMP-activated protein kinase activation with AICAR amplifies counterregulatory responses to hypoglycemia in a rodent model of type 1 diabetes Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2009; 296(6): R1702 - R1708. [Abstract] [Full Text] [PDF]

				I. Quesada, E. Tuduri, C. Ripoll, and A. Nadal Physiology of the pancreatic {alpha}-cell and glucagon secretion: role in glucose homeostasis and diabetes J. Endocrinol., October 1, 2008; 199(1): 5 - 19. [Abstract] [Full Text] [PDF]

				P. Bansal and Q. Wang Insulin as a physiological modulator of glucagon secretion Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E751 - E761. [Abstract] [Full Text] [PDF]

				L. S. Farhy, Z. Du, Q. Zeng, P. P. Veldhuis, M. L. Johnson, K. L. Brayman, and A. L. McCall Amplification of pulsatile glucagon counterregulation by switch-off of {alpha}-cell-suppressing signals in streptozotocin-treated rats Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E575 - E585. [Abstract] [Full Text] [PDF]