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Independent and combined effects of acute physiological hyperglycaemia and hyperinsulinaemia on metabolic gene expression in human skeletal muscle.
MedLine Citation:
PMID:  23316693     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Physiological hyperglycaemia and hyperinsulinaemia are strong modulators of gene expression, which underpins some of their well known effects on insulin action and energy metabolism. The aim of this study was to examine whether acute in vivo exposure of healthy humans to hyperinsulinaemia and hyperglycaemia have independent or additive effects on expression of key metabolic genes in skeletal muscle. On 3 randomised occasions, 7 young subjects underwent a 4 h (i) hyperinsulinaemic (50 mU . m-2 . min-1) hyperglycaemic (10 mmol/l) clamp (HIHG), (ii) hyperglycaemic (10 mmol/l) euinsulinaemic (5 mU . m-2 . min-1) clamp (LIHG) and (iii) hyperinsulinaemic (50 mU . m-2 . min-1) euglycaemic (4.5 mmol/l) clamp (HING). Muscle biopsies were obtained before and after each clamp for the determination of expression of genes involved in energy metabolism, and phosphorylation of key insulin signalling proteins. Hyperinsulinaemia and hyperglycaemia exerted independent effects with similar direction of modulation on Phosphatidylinositol 3-kinase, regulatory 1 (PIK3R1), Liver X receptor a (LXRa), Pyruvate dehydrogenase kinase 4 (PDK4) and Forkhead transcription factor 1A (FOXO1) and produced an additive effect on PIK3R1, the gene that encodes the p85a subunit of PIK3 in human skeletal muscle. Acute hyperglycaemia itself altered the expression of genes involved in fatty acid transport and oxidation [Fatty acid transporter (CD36), long chain acyl-coenzyme A dehydrogenase (LCAD) and FOXO1], and lipogenesis [LXRa, Carbohydrate response element binding protein (ChREBP), ATP binding cassette transporter A1 (ABCA1), Glucose-6-phosphate dehydrogenase (G6PD)]. Surperimposing hyperinsulinaemia on hyperglycaemia modulated a number of genes involved in insulin signalling, glucose metabolism and intracellular lipid accumulation and exerted an additive effect on PIK3R1. These may be early molecular events that precede the development of glucolipotoxicity and insulin resistance normally associated with more prolonged periods of hyperglycaemia and hyperinsulinaemia.
Authors:
Kostas Tsintzas; Luke Norton; Kamal Chokkalingam; Nusrat Nizamani; Scott Cooper; Francis Stephens; Rudi Billeter; Andrew Bennett
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-15
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  -     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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