CL 316, 243 mediated reductions in blood glucose are enhanced in RIP140-/-mice independent of alterations in lipolysis.
The β-3 adrenergic agonist CL 316, 243 acutely lowers blood glucose through a mechanism thought to involve fatty-acid induced insulin release. The purpose of this study was to determine if ablation of the nuclear receptor, receptor-inactivating protein 140 (RIP140), altered this response. Here, we used a single injection of CL 316, 243 (1 mg/kg) and found that whole body RIP140-/-mice had a greater decline in blood glucose over 2 h. This occurred alongside increased hexokinase II (HKII) protein content in adipose tissue and skeletal muscle, but independent of changes in circulating insulin or indices of lipolysis. These data indicate that RIP140 has a unique role in the acute effect of β-3 adrenergic receptor activation using CL 316, 243.
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Willem T
WT
Peppler
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Paula M
PM
Miotto
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Graham P
GP
Holloway
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada. Electronic address: dcwright@uoguelph.ca.
David C
DC
Wright
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*; D000078723:Nuclear Receptor Interacting Protein 1; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D058667:Adrenergic beta-3 Receptor Agonists; D001786:Blood Glucose; D004149:Dioxoles; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D006593:Hexokinase
Adipose; CL 316, 243; Glucose; Lipolysis; Mouse; RIP140