Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia.
Rats that develop diet-induced obesity (DIO) on a 31% fat [high-energy (HE)] diet have defective sensing and responding to altered glucose levels compared with diet-resistant (DR) rats. Thus we postulated that they would also have defective counterregulatory responses (CRR) to insulin-induced hypoglycemia (IIH). Chow-fed selectively bred DIO and DR rats underwent three sequential 60-min bouts of IIH separated by 48 h. Glucose levels fell comparably, but DIO rats had 22-29% lower plasma epinephrine (Epi) levels during the first two bouts than DR rats. By the third trial, despite comparable Epi levels, DIO rats had lower 30-min glucose levels and rebounded less than DR rats 85 min after intravenous glucose. Although DIO rats gained more carcass and fat weight after 4 wk on an HE diet than DR rats, they were unaffected by prior IIH. Compared with controls, DR rats with prior IIH and HE diet had higher arcuate nucleus neuropeptide Y (50%) and proopiomelanocortin (POMC; 37%) mRNA and an inverse correlation (r = 0.85; P = 0.004) between POMC expression and body weight gain on the HE diet. These data suggest that DIO rats have a preexisting defect in their CRR to IIH but that IIH does not affect the expression of their hypothalamic neuropeptides or weight gain as it does in DR rats.
Tkacs
Nancy C
NC
University of Pennsylvania School of Nursing, Philadelphia 19104-6096, USA.
Levin
Barry E
BE
D000273:Adipose Tissue / Q000254:growth & development; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D004032:Diet; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization; D007328:Insulin; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015430:Weight Gain / Q000502:physiology
D001786:Blood Glucose; D002395:Catecholamines; D007004:Hypoglycemic Agents; D007328:Insulin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D019344:Lactic Acid; D011333:Pro-Opiomelanocortin