Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 287; no. 5; pp. R1110 - R1115
• Main Authors: Tkacs, Nancy C, Levin, Barry E
• Format: Journal Article
• Language: English
• Published: United States 01.11.2004
• Subjects: Adipose Tissue - growth & development; Animals; Arcuate Nucleus of Hypothalamus - metabolism; Blood Glucose - metabolism; Body Composition - genetics; Body Composition - physiology; Catecholamines - blood; Diet; Homeostasis - genetics; Homeostasis - physiology; Hypoglycemia - chemically induced; Hypoglycemia - physiopathology; Hypoglycemic Agents; Hypothalamus - metabolism; In Situ Hybridization; Insulin; Lactic Acid - blood; Male; Neuropeptide Y - biosynthesis; Obesity - genetics; Obesity - physiopathology; Organ Size - physiology; Pro-Opiomelanocortin - biosynthesis; Rats; RNA, Messenger - biosynthesis; Weight Gain - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00312.2004

1 University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania 19104-6096; 2 Neurology Service, Veterans Affairs Medical Center, East Orange 07018-1095; and 3 Department of Neurology and Neurosciences, New Jersey Medical School, Newark, New Jersey 07103 Submitted 12 May 2004 ; accepted in final form 27 July 2004 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. diet-induced obesity; epinephrine; norepinephrine; neuropeptide Y; proopiomelanocortin; hypoglycemia-associated autonomic failure Address for reprint requests and other correspondence: B. E. Levin, Neurology Service (127C), VA Medical Center, E. Orange, NJ 07018-1095 (E-mail: levin{at}umdnj.edu )