PMID: 15677492Jan 29, 2005

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside causes acute hepatic insulin resistance in vivo

Diabetes
R Richard PencekDavid H Wasserman

Abstract

The infusion of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) causes a rise in tissue concentrations of the AMP analog 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranotide (ZMP), which mimics an elevation of cellular AMP levels. The purpose of this work was to determine the effect of raising hepatic ZMP levels on hepatic insulin action in vivo. Dogs had sampling and infusion catheters as well as flow probes implanted 16 days before an experiment. After an 18-h fast, blood glucose was 82 +/- 1 mg/dl and basal net hepatic glucose output 1.5 +/- 0.2 mg . kg(-1) . min(-1). Dogs received portal venous glucose (3.2 mg . kg(-1) . min(-1)), peripheral venous somatostatin, and basal portal venous glucagon infusions from -90 to 60 min. Physiological hyperinsulinemia was established with a portal insulin infusion (1.2 mU . kg(-1) . min(-1)). Peripheral venous glucose infusion was used to clamp arterial blood glucose at 150 mg/dl. Starting at t = 0 min, dogs received portal venous AICAR infusions of 0, 1, or 2 mg . kg(-1) . min(-1). Net hepatic glucose uptake was 2.4 +/- 0.5 mg . kg(-1) . min(-1) (mean of all groups) before t = 0 min. In the absence of AICAR, net hepatic glucose uptake was 1.9 +/- 0.4 mg . kg(-1) . min(-...Continue Reading

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Citations

Sep 1, 2005·Canadian Journal of Applied Physiology = Revue Canadienne De Physiologie Appliquée·R Richard PencekDavid H Wasserman
Aug 8, 2009·The Journal of Clinical Investigation·Eric D BerglundDavid H Wasserman
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Related Concepts

5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamide monophosphate
Cyclic AMP, (R)-Isomer
Ba 2756
Blood Glucose
Canis familiaris
Glycolysis
Compensatory Hyperinsulinemia
Intravenous Infusion Procedures
Insulin Sensitivity
Liver

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