Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice

American Journal of Physiology. Endocrinology and Metabolism
Lauren JacobsonOwen P McGuinness

Abstract

Hypoglycemia-induced counterregulatory failure is a dangerous complication of insulin use in diabetes mellitus. Controlled hypoglycemia studies in gene knockout models, which require the use of mice, would aid in identifying causes of defective counterregulation. Because stress can influence counterregulatory hormones and glucose homeostasis, we developed glucose clamps with remote blood sampling in conscious, unrestrained mice. Male C57BL/6 mice implanted with indwelling carotid artery and jugular vein catheters were subjected to 2 h of hyperinsulinemic glucose clamps 24 h apart, with a 6-h fast before each clamp. On day 1, blood glucose was maintained (euglycemia, 178 +/- 4 mg/dl) or decreased to 62 +/- 1 mg/dl (hypoglycemia) by insulin (20 mU x kg(-1) x min(-1)) and variable glucose infusion. Donor blood was continuously infused to replace blood sample volume. Baseline plasma epinephrine (32 +/- 8 pg/ml), corticosterone (16.1 +/- 1.8 microg/dl), and glucagon (35 +/- 3 pg/ml) were unchanged during euglycemia but increased significantly during hypoglycemia, with a glycemic threshold of approximately 80 mg/dl. On day 2, all mice underwent a hypoglycemic clamp (blood glucose, 64 +/- 1 mg/dl). Compared with mice that were euglyce...Continue Reading

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Citations

Jun 19, 2013·Respiratory Physiology & Neurobiology·P ChalachevaM C K Khoo
Feb 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lina Sabra-MakkePascale Bossard
Feb 2, 2006·American Journal of Physiology. Endocrinology and Metabolism·Lauren JacobsonOwen P McGuinness
Jul 30, 2009·American Journal of Physiology. Endocrinology and Metabolism·Owen P McGuinnessDavid H Wasserman
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