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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/E928    most recent 00063.2006v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Chen, S.-S. Articles by McGuinness, O. P. Search for Related Content PubMed PubMed Citation Articles by Chen, S.-S. Articles by McGuinness, O. P.

Glucagon chronically impairs hepatic and muscle glucose disposal

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 7 February 2006 ; accepted in final form 26 November 2006

Defects in insulin secretion and/or action contribute to the hyperglycemia of stressed and diabetic patients, and we hypothesize that failure to suppress glucagon also plays a role. We examined the chronic impact of glucagon on glucose uptake in chronically catheterized conscious depancreatized dogs placed on 5 days of nutritional support (NS). For 3 days of NS, a variable intraportal infusion of insulin was given to maintain isoglycemia (120 mg/dl). On day 3 of NS, animals received a constant low infusion of insulin (0.4 mU·kg^–1·min^–1) and either no glucagon (CONT), basal glucagon (0.7 ng·kg^–1·min^–1; BasG), or elevated glucagon (2.4 ng·kg^–1·min^–1; HiG) for the remaining 2 days. Glucose in NS was varied to maintain isoglycemia. An additional group (HiG + I) received elevated insulin (1 mU·kg^–1·min^–1) to maintain glucose requirements in the presence of elevated glucagon. On day 5 of NS, hepatic substrate balance was assessed. Insulin and glucagon levels were 10 ± 2, 9 ± 1, 7 ± 1, and 24 ± 4 µU/ml, and 24 ± 5, 39 ± 3, 80 ± 11, and 79 ± 5 pg/ml, CONT, BasG, HiG, and HiG + I, respectively. Glucagon infusion decreased the glucose requirements (9.3 ± 0.1, 4.6 ± 1.2, 0.9 ± 0.4, and 11.3 ± 1.0 mg·kg^–1·min^–1). Glucose uptake by both hepatic (5.1 ± 0.4, 1.7 ± 0.9, –1.0 ± 0.4, and 1.2 ± 0.4 mg·kg^–1·min^–1) and nonhepatic (4.2 ± 0.3, 2.9 ± 0.7, 1.9 ± 0.3, and 10.2 ± 1.0 mg·kg^–1·min^–1) tissues decreased. Additional insulin augmented nonhepatic glucose uptake and only partially improved hepatic glucose uptake. Thus, glucagon impaired glucose uptake by hepatic and nonhepatic tissues. Compensatory hyperinsulinemia restored nonhepatic glucose uptake and partially corrected hepatic metabolism. Thus, persistent inappropriate secretion of glucagon likely contributes to the insulin resistance and glucose intolerance observed in obese and diabetic individuals.

glycogen; glucokinase; muscle