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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/E1131    most recent 00518.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Christopher, M. Articles by Alford, F. P. Search for Related Content PubMed PubMed Citation Articles by Christopher, M. Articles by Alford, F. P.

TRANSLATIONAL PHYSIOLOGY

Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion

¹Departments of Endocrinology and Diabetes and Medicine, St. Vincent's Hospital, Fitzroy; ²Departments of Endocrinology and Diabetes and Medicine, University of Melbourne, Parkville; ³St. Vincent's Institute of Medical Research, St. Vincent's Hospital, Fitzroy; and ⁴School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia

Submitted 26 October 2005 ; accepted in final form 28 April 2006

AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1--D-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FA_OX) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0–150 min), fasting dogs (n = 8) were infused with [3-³H]glucose followed by either 2-h saline or AICAR (1.5–2.0 mg·kg^–1·min^–1) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FA_OX blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (R_{d tissue}), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR_g) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACCpSer²²¹) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R_{d tissue} responses were markedly attenuated, but MCR_g and GF increased significantly. SkM substrates were unchanged, but ACCpSer²²¹ rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA_ox blockade.

5-aminoimidazole-4-carboxamide-1--D-ribofuranoside; 5-aminoimidazole-4-carboxamide-1--D-ribosyl monophosphate; acetyl-coenzyme A carboxylase; phosphorylation; skeletal muscle; muscle biopsy; dogs

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