Lewitt M S, Brismar K, Wang J, Wivall-Helleryd I L, Sindelar P, Gonzalez F J, Bergman T, Bobek G A
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Growth Horm IGF Res. 2001 Oct;11(5):303-13. doi: 10.1054/ghir.2001.0247.
Peroxisome proliferator-activated receptor alpha (PPARalpha) plays a central role in glucose and lipid homeostasis. Mice lacking PPARalpha(-/-) have a sexually dimorphic phenotype. We have characterized the IGF system in wild type and PPARalpha-/- mice. In normal mice fasting IGF-I and the IGFBP-3 ternary complex were 2-fold higher in males than in females. PPARalpha influenced the IGF/IGFBP response to feeding, particularly in males. Compared to wild type, male PPARalpha-/- mice had 40% lower total fasting IGF-I concentrations, decreased ALS and less IGFBP-3 ternary complex formation, but within 4 h of refeeding there was an increase in IGF-I and IGFBP-3 ternary complex to values similar to controls. Circulating IGFBP protease activity was induced in male PPARalpha-/- mice during refeeding. IGFBP-1 and insulin concentrations were higher in males than females, and were increased by PPARalpha knockout, suggesting significant hepatic insulin resistance. We speculate that gender differences in the IGF system contribute to the PPARalpha-/- phenotype.
过氧化物酶体增殖物激活受体α（PPARα）在葡萄糖和脂质稳态中起核心作用。缺乏PPARα的小鼠（PPARα-/-）具有性别二态性表型。我们已经对野生型和PPARα-/-小鼠的胰岛素样生长因子（IGF）系统进行了表征。在正常小鼠中，禁食状态下雄性小鼠的IGF-I和IGFBP-3三元复合物水平比雌性小鼠高2倍。PPARα影响IGF/IGFBP对进食的反应，特别是在雄性小鼠中。与野生型相比，雄性PPARα-/-小鼠的空腹总IGF-I浓度降低了40%，酸性不稳定亚基（ALS）减少，IGFBP-3三元复合物形成减少，但在重新进食4小时内，IGF-I和IGFBP-3三元复合物增加至与对照组相似的值。重新进食期间，雄性PPARα-/-小鼠的循环IGFBP蛋白酶活性被诱导。雄性小鼠的IGFBP-1和胰岛素浓度高于雌性小鼠，并且通过PPARα基因敲除而增加，提示存在明显的肝脏胰岛素抵抗。我们推测IGF系统中的性别差异导致了PPARα-/-表型。
