Petterson J A, Dunshea F R, Ehrhardt R A, Bell A W
Department of Animal Science, Cornell University, Ithaca, NY 14853-4801.
J Nutr. 1993 Jul;123(7):1286-95. doi: 10.1093/jn/123.7.1286.
Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.
未怀孕和怀孕后期的双胎母羊被分别给予饲料，以使母体组织维持零能量平衡（正常喂养组）或维持在该水平的50%（低喂养组），持续数周。在基础条件下测量全身葡萄糖代谢动力学，并采用高胰岛素-正常血糖钳夹技术来确定全身葡萄糖利用的几个指标以及内源性葡萄糖生成的胰岛素剂量反应曲线。怀孕会增加，而营养不良会降低基础葡萄糖进入率（GER）、葡萄糖代谢清除率（GMCR）和胰岛素非依赖性葡萄糖利用（IIGU）。怀孕母羊的IIGU持续增加，与先前对子宫葡萄糖摄取的估计相当。怀孕导致GER、GMCR、维持正常血糖的稳态葡萄糖输注率（SSGIR）和胰岛素依赖性葡萄糖利用（IDGU）对胰岛素的50%最大反应（ED50）时的血浆浓度更高。这些变化在低喂养的怀孕母羊中尤为明显。这些变量对胰岛素最大反应（Rmax）的影响相对较小（GMCR、IDGU）或不显著（GER、SSGIR）。由于营养不良，胰岛素诱导的内源性葡萄糖生成的最大抑制作用显著降低；怀孕对该反应的Rmax和ED50均无影响。怀孕后期母羊的胰岛素抵抗主要是由于（可能）外周组织中胰岛素敏感性降低，这意味着受体功能或受体后早期信号转导发生了改变。
