title: Ghrelin inhibits insulin resistance induced by glucotoxicity and lipotoxicity in cardiomyocyte.
abstract: Ghrelin has wide effects on cardiovascular and endocrine system. The aims of this study are to investigate the direct damage effect of high glucose and high palmitate on cardiomyocyte, and to study the effect of ghrelin on insulin resistance induced by glucotoxicity/lipotoxicity in cardiomyocyte and the possible mechanism underlying the cardioprotective activities of ghrelin. The changes of [(3)H]-2-deoxy-d-glucose ((3)H-G) intake rates were detected by isotope tracer method and the gene expressions in insulin signal transduction pathway were detected by real-time PCR and Western blot assay. The (3)H-G intake rate significantly reduced in high glucose (25mmol/l) or high palmitate (0.5mmol/l) treated primary rat ventricular myocytes. After the treatment of ghrelin (10(-7)mol/l), the (3)H-G intake rate recovered to the normal level. In addition, the phosphorylation of AKT occurred in 10min and was the highest in 30min after the stimulation with ghrelin, which can be blocked by phosphoinositide 3-kinase (PI3K) inhibitor, LY2940002. Ghrelin also increased the mRNA levels of glucose transporter 4 (GLUT4), peroxisome proliferators (PPARr) and AMP activated protein kinase (AMPK) genes in insulin signal transduction pathway. These results indicate that the direct damage of high glucose and high palmitate on cardiomyocyte might be through insulin resistance (IR). Ghrelin can inhibit gluco/lipotoxicity induced insulin resistance by PI3K/AKT pathway. This may provide a clue for therapy for myocardial disease in diabetes mellitus.
authors.affiliation: Department of Geraeology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Cao
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Guoliang
authors.initials: G
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D054439:Ghrelin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology* / Q000633:toxicity; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007333:Insulin Resistance; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics; D019308:Palmitic Acid / Q000494:pharmacology* / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D055372:AMP-Activated Protein Kinases; D002867:Chromones; D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D054439:Ghrelin; D005947:Glucose; D051275:Glucose Transporter Type 4; D009025:Morpholines; D047495:PPAR gamma; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C495694:Slc2a4 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one