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

Christopher, Michael, Rantzau, Christian, Chen, Zhi-Ping, Snow, Rodney, Kemp, Bruce and Alford, Frank P. 2006, Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion, American journal of physiology: endocrinology and metabolism, vol. 291, no. 5, pp. E1311-E1140.

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Title Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion
Author(s) Christopher, Michael
Rantzau, Christian
Chen, Zhi-Ping
Snow, Rodney
Kemp, Bruce
Alford, Frank P.
Journal name American journal of physiology: endocrinology and metabolism
Volume number 291
Issue number 5
Start page E1311
End page E1140
Publisher American Physiological Society
Place of publication Bethesda, Md.
Publication date 2006
ISSN 0193-1849
1522-1555
Keyword(s) 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
5-aminoimidazole-4-carboxamide-1-beta-D-ribosyl monophosphate
acetyl-coenzyme A carboxylase
phosphorylation
skeletal muscle
muscle biopsy
dogs
Summary 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-ß-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 (FAOX) 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 FAOX 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 (Rd tissue), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCRg) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC~pSer221) 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 Rd tissue responses were markedly attenuated, but MCRg and GF increased significantly. SkM substrates were unchanged, but ACC~pSer221 rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FAox blockade.
Language eng
Field of Research 060104 Cell Metabolism
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2006, American Physiological Society.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30008962

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