title: STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.
abstract: Effects of streptozotocin (STZ)-induced diabetes and insulin on opioid peptide gene expression were examined in rats. In experiment 1, three groups were administered STZ (75 mg/kg ip single injection). Two groups were killed at either 2 or 4 wk. In the third group, insulin treatment (7.0 IU/kg x 1 day for 3 wk) was initiated 1 wk after STZ injection. STZ induced hyperphagia and reduced weight gain. Insulin decreased food intake and increased body weight relative to diabetes. Proopiomelanocortin (POMC) mRNA in arcuate nucleus (Arc) and pituitary decreased in diabetes and normalized after insulin treatment. Prodynorphin (proDyn) mRNA increased in diabetes and normalized in the pituitary after insulin but not in the Arc. Diabetes did not alter proenkephalin (proEnk) expression in the Arc or pituitary, nor dynorphin A1-17 or beta-endorphin in paraventricular nucleus (PVN). alpha-Melanocyte-stimulating hormone (alpha-MSH) peptide levels were decreased in the PVN and normalized following insulin treatment. Diabetes increased Arc neuropeptide Y mRNA, and insulin suppressed this increase. In experiment 2, insulin (2.5 IU/kg sc) daily for 1 wk in normal rats increased Arc POMC mRNA, but not proDyn and proEnk mRNA. These results suggest that Arc POMC expression and PVN alpha-MSH peptide levels decrease in diabetes. Also, insulin may influence Arc and pituitary POMC activity in neurons that regulate energy metabolism.
authors.affiliation: Minnesota Obesity Center and Research Service, Veterans Affairs Medical Center, Minneapolis 55417, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Kim
authors.forename: M K
authors.initials: MK
authors.lastname: Grace
authors.forename: C C
authors.initials: CC
authors.lastname: Welch
authors.forename: C J
authors.initials: CJ
authors.lastname: Billington
authors.forename: A S
authors.initials: AS
authors.lastname: Levine
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000378:metabolism; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004745:Enkephalins; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D009478:Neuropeptide Y; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; C029992:proenkephalin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; C033660:preproenkephalin