Enhanced hypothalamic AMP-activated protein kinase activity contributes to hyperphagia in diabetic rats.
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.
Namkoong
Churl
C
Asan Institute for Life Sciences, Ulsan University College of Medicine, Poognap-dong, Songpa-gu, Seoul 138-736, Korea.
Kim
Min Seon
MS
Jang
Pil Geum
PG
Han
Sung Min
SM
Park
Hye Sun
HS
Koh
Eun Hee
EH
Lee
Woo Je
WJ
Kim
Jong Yeon
JY
Park
In Sun
IS
Park
Joong Yeol
JY
Lee
Ki Up
KU
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
D007328:Insulin; D020738:Leptin; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases