title: Ghrelin stimulates insulin-induced glucose uptake in adipocytes.
abstract: The gastric and hypothalamic hormone ghrelin is the endogenous agonist of the growth hormone secretagogue receptor GHS-R1(a). Ghrelin stimulates growth hormone release and appetite via the hypothalamus. However, putative direct peripheral effects of ghrelin remain poorly understood. Rat adipose tissue expresses GHS-R1(a) mRNA, suggesting ghrelin may directly influence adipocyte function. We have investigated the effects of ghrelin on insulin-stimulated glucose uptake in isolated white adipocytes in vitro. RT-PCR confirmed the expression of GHS-R1(a) mRNA in epididymal adipose tissue. However, GHS-R1(a) expression was not detected in the peri-renal fat pads. Ghrelin increased insulin-stimulated deoxyglucose uptake in isolated white adipocytes extracted from the epididymal fat pads of male Wistar rats. Ghrelin 1000 nM significantly increased deoxyglucose uptake by 55% in the presence of 0.1 nM insulin. However, ghrelin administration in the absence of insulin had no effect on adipocyte deoxyglucose uptake, suggesting that ghrelin acts synergistically with insulin. Des-acyl ghrelin, a major circulating non-octanylated form of ghrelin, had no effect on insulin-stimulated glucose uptake. Furthermore, acylated ghrelin had no effect on deoxyglucose uptake in adipocytes from peri-renal fat pads suggesting that ghrelin may influence glucose uptake via the GHS-R1(a). Ghrelin therefore appears to directly potentiate adipocyte insulin-stimulated glucose uptake in selective adipocyte populations. Ghrelin may play a role in adipocyte regulation of glucose homeostasis.
authors.affiliation: Department of Metabolic Medicine, Nutrition and Dietetic Research Group, Imperial College Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 ONN, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Patel
authors.forename: S A
authors.initials: SA
authors.lastname: Stanley
authors.forename: K G
authors.initials: KG
authors.lastname: Murphy
authors.forename: G S
authors.initials: GS
authors.lastname: Frost
authors.forename: J V
authors.initials: JV
authors.lastname: Gardiner
authors.forename: A S
authors.initials: AS
authors.lastname: Kent
authors.forename: N E
authors.initials: NE
authors.lastname: White
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D054440:Receptors, Ghrelin
chemical_list: D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D005947:Glucose