title: Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.
abstract: Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide expressed in the nervous system and in endocrine cells, e.g. in pancreatic islets. CART deficient mice exhibit islet dysfunction, impaired insulin secretion and increased body weight. A mutation in the CART gene in humans is associated with reduced metabolic rate, obesity and diabetes. Furthermore, CART is upregulated in islets of type-2 diabetic rats and regulates islet hormone secretion in vitro. While the function of CART in the nervous system has been extensively studied, there is no information on its expression or function in white adipose tissue. CART mRNA and protein were found to be expressed in both subcutaneous and visceral white adipose tissue from rat and man. Stimulating rat primary adipocytes with CART significantly potentiated isoprenaline-induced lipolysis, and hormone sensitive lipase activation (phosphorylation of Ser 563). On the other hand, CART significantly potentiated the inhibitory effect of insulin on isoprenaline-induced lipolysis. CART inhibited insulin-induced glucose uptake and lipogenesis, which was associated with inhibition of PKB phosphorylation. In conclusion, CART is a novel constituent of human and rat adipocytes and affects several biological processes central in both lipid- and glucose homeostasis. Depending on the surrounding conditions, the effects of CART are insulin-like or insulin-antagonistic.
authors: Department of Experimental Medical Sciences, Lund University Diabetes Centre, BMC, Sölvegatan 19, 221 84 Lund, Sweden. elin.banke@med.lu.se
authors: E
authors: E
authors: Banke
authors: M
authors: M
authors: Riva
authors: L
authors: L
authors: Shcherbina
authors: N
authors: N
authors: Wierup
authors: E
authors: E
authors: Degerman
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology; D050356:Lipid Metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D005947:Glucose; D007545:Isoproterenol