Laychock S G, Vadlamudi S, Patel M S
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214, USA.
Am J Physiol. 1995 Oct;269(4 Pt 1):E739-44. doi: 10.1152/ajpendo.1995.269.4.E739.
Neonatal rat pups were artificially reared on isocaloric diets high in carbohydrate (HC) or high in fat (HF) or were naturally reared on mother's milk (MF). The HC adult rats were hyperinsulinemic, normoglycemic, and obese. This study investigates pancreatic islet insulin release (IR) of the adult first-generation (1-) diet-regulated animals and their second-generation (2-) progeny. Male rat 1-HC islets had higher basal IR than either 1-MF or 1-HF control groups. In addition, glucose (17 mM) failed to increase IR above basal values in 1-HC islets, whereas it stimulated IR in 1-MF and 1-HF islets. Similar secretory responses were evoked by 2-ketoisocaproic acid (2-KIC). Female rat 1-MF and 1-HF islets also had higher glucose-stimulated IR compared with 1-HC islets. Male rat 2-HC islets had higher basal IR and reduced sensitivity to glucose and 2-KIC compared with 2-MF islets, which coincided with hyperinsulinemia. Glyceraldehyde-3-phosphate dehydrogenase activity in 1-HC and 2-HC islets was higher than in MF islets. These data suggest that basal IR is higher in islets isolated from animals reared as neonates on a diet high in carbohydrate. Alterations in beta-cell metabolism and secretion probably contribute to the hyperinsulinemia, reduced glucose sensitivity, and glucose intolerance characteristic of this rat model.
新生大鼠幼崽分别用高碳水化合物（HC）或高脂肪（HF）的等热量饮食人工饲养，或用母乳（MF）自然饲养。成年HC大鼠表现为高胰岛素血症、血糖正常和肥胖。本研究调查了第一代（1-）饮食调节动物及其第二代（2-）后代成年大鼠胰岛的胰岛素释放（IR）情况。雄性大鼠1-HC胰岛的基础IR高于1-MF或1-HF对照组。此外，葡萄糖（17 mM）未能使1-HC胰岛的IR高于基础值，而它能刺激1-MF和1-HF胰岛的IR。2-酮异己酸（2-KIC）也能引发类似的分泌反应。与1-HC胰岛相比，雌性大鼠1-MF和1-HF胰岛的葡萄糖刺激IR也更高。与2-MF胰岛相比，雄性大鼠2-HC胰岛的基础IR更高，对葡萄糖和2-KIC的敏感性降低，这与高胰岛素血症一致。1-HC和2-HC胰岛中的甘油醛-3-磷酸脱氢酶活性高于MF胰岛。这些数据表明，从新生时用高碳水化合物饮食饲养的动物分离出的胰岛基础IR更高。β细胞代谢和分泌的改变可能导致了该大鼠模型的高胰岛素血症、葡萄糖敏感性降低和葡萄糖不耐受。
