Tkacs Nancy C, Levin Barry E
University of Pennsylvania School of Nursing, Philadelphia 19104-6096, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1110-5. doi: 10.1152/ajpregu.00312.2004.
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.
与饮食抵抗（DR）大鼠相比，在31%脂肪[高能量（HE）]饮食下发生饮食诱导性肥胖（DIO）的大鼠在感知和应对血糖水平变化方面存在缺陷。因此，我们推测它们对胰岛素诱导的低血糖（IIH）的反调节反应（CRR）也存在缺陷。用普通饲料喂养的选择性繁殖的DIO和DR大鼠经历了三次连续60分钟的IIH发作，每次发作间隔48小时。血糖水平下降程度相当，但在最初两次发作期间，DIO大鼠的血浆肾上腺素（Epi）水平比DR大鼠低22%-29%。到第三次试验时，尽管Epi水平相当，但DIO大鼠在静脉注射葡萄糖后30分钟的血糖水平较低，且在85分钟后的回升幅度小于DR大鼠。尽管在HE饮食4周后，DIO大鼠比DR大鼠增加了更多的胴体和脂肪重量，但它们不受先前IIH的影响。与对照组相比，先前经历过IIH且采用HE饮食的DR大鼠的弓状核神经肽Y（50%）和阿黑皮素原（POMC；37%）mRNA水平较高，且POMC表达与HE饮食期间体重增加呈负相关（r = 0.85；P = 0.004）。这些数据表明，DIO大鼠对IIH的CRR预先存在缺陷，但IIH并不像在DR大鼠中那样影响它们下丘脑神经肽的表达或体重增加。
