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.
University of Pennsylvania School of Nursing, Philadelphia 19104-6096, USA.
Nancy C
NC
Tkacs
Barry E
BE
Levin
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