title: Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats.
abstract: AMP-activated protein kinase (AMPK) acts as a cellular energy sensor, being activated during states of low energy charge. Hypothalamic AMPK activity is altered by hormonal and metabolic signals and mediates the feeding response. To determine the effect of diabetes on hypothalamic AMPK activity, we assayed this activity in streptozotocin (STZ)-induced diabetic rats. Compared with control rats, STZ-induced diabetic rats had significant hyperphagia and weight loss. Hypothalamic AMPK phosphorylation and alpha2-AMPK activity were higher and acetyl-CoA carboxylase activity was lower in diabetic rats than in control rats. Chronic insulin treatment or suppression of hypothalamic AMPK activity completely prevented diabetes-induced changes in food intake as well as in hypothalamic AMPK activity and mRNA expression of neuropeptide Y and proopiomelanocortin. Plasma leptin and insulin levels were profoundly decreased in diabetic rats. Intracerebroventricular administration of leptin and insulin reduced hyperphagia and the enhanced hypothalamic AMPK activity in diabetic rats. These data suggest that leptin and insulin deficiencies in diabetes lead to increased hypothalamic AMPK activity, which contributes to the development of diabetic hyperphagia.
authors.affiliation: Asan Institute for Life Sciences, Ulsan University College of Medicine, Poognap-dong, Songpa-gu, Seoul 138-736, Korea.
authors.forename: Churl
authors.initials: C
authors.lastname: Namkoong
authors.forename: Min Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Pil Geum
authors.initials: PG
authors.lastname: Jang
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: Jong Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: In Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Joong Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Ki Up
authors.initials: KU
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D002149:Energy Intake; D018014:Gene Transfer Techniques; D016259:Genes, myc / Q000235:genetics; D006963:Hyperphagia / Q000201:enzymology*; D007031:Hypothalamus / Q000201:enzymology* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009929:Organ Size; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss
chemical_list: D007328:Insulin; D020738:Leptin; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases