Lee Joo-Won, Romsos Dale R
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824-1224, USA.
Exp Biol Med (Maywood). 2003 Feb;228(2):183-7. doi: 10.1177/153537020322800208.
Leptin-deficient Lep(ob)/Lep(ob) mice exhibit elevations in plasma insulin early in development. The present study tested the hypothesis that absence of leptin during neonatal development permanently programs islets from these mice to hypersecrete insulin. Administration of leptin for 8 days to young adult Lep(ob)/Lep(ob) mice normalized their food intake, plasma insulin concentration, and insulin secretion in response to glucose, acetylcholine, and leptin. Restriction of food intake per se of Lep(ob)/Lep(ob) mice lowered, but did not normalize, plasma insulin concentrations. Food-restricted Lep(ob)/Lep(ob) mice continued to hypersecrete insulin in response to glucose, but islets from these mice did not hyperrespond to acetylcholine or respond to leptin as occurs in ad libitum-fed Lep(ob)/Lep(ob) mice. We conclude that neonatal leptin deficiency does not permanently program islets from mice to hypersecrete insulin. The hyperphagia associated with leptin deficiency contributes substantially to the hypersecretion of insulin, but leptin also appears to have more direct effects on regulation of insulin secretion.
瘦素缺乏的Lep(ob)/Lep(ob)小鼠在发育早期血浆胰岛素水平升高。本研究检验了以下假设：新生期发育过程中缺乏瘦素会使这些小鼠的胰岛永久性地编程为高分泌胰岛素。给年轻的成年Lep(ob)/Lep(ob)小鼠注射瘦素8天，可使其食物摄入量、血浆胰岛素浓度以及对葡萄糖、乙酰胆碱和瘦素的胰岛素分泌恢复正常。Lep(ob)/Lep(ob)小鼠本身限制食物摄入量可降低血浆胰岛素浓度，但不能使其恢复正常。食物受限的Lep(ob)/Lep(ob)小鼠在对葡萄糖的反应中继续高分泌胰岛素，但其胰岛对乙酰胆碱没有高反应，也不像自由进食的Lep(ob)/Lep(ob)小鼠那样对瘦素有反应。我们得出结论，新生期瘦素缺乏不会使小鼠胰岛永久性地编程为高分泌胰岛素。与瘦素缺乏相关的食欲亢进在很大程度上导致了胰岛素的高分泌，但瘦素似乎对胰岛素分泌的调节也有更直接的作用。
