Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism.

Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism.
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DOI:
10.2337/db08-1054
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发表时间:
2009-04
期刊:
影响因子:
7.7
通讯作者:
Kahn CR
Kahn CR
中科院分区:
医学1区
文献类型:
--
作者:
Macotela Y;Boucher J;Tran TT;Kahn CR

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研究雄性和雌性小鼠不同脂肪库之间脂肪细胞的胰岛素敏感性和葡萄糖代谢有何差异,以及性类固醇如何导致这些差异。分离来自正常、去势或类固醇植入动物的腹内/性腺周围(PG)和皮下(SC)脂肪组织的脂肪细胞,并分析胰岛素敏感性和葡萄糖代谢的差异。与男性相比,女性 PG 和 SC 库中的脂肪细胞的脂肪生成率有所增加。在女性中,腹内 PG 脂肪细胞比 SC 脂肪细胞对胰岛素更敏感,并且比任一储存库的男性脂肪细胞对胰岛素更敏感。当受到低生理浓度的胰岛素刺激时,雌性 PG 脂肪细胞的 Akt 和细胞外信号相关激酶 (ERK) 磷酸化和脂肪生成显着增加,而雄性脂肪细胞仅在较高的胰岛素浓度下才表现出激活。女性脂肪细胞中涉及葡萄糖和脂质代谢的多个基因的 mRNA/蛋白质水平较高。去势后,雄性小鼠的脂肪细胞表现出胰岛素敏感性增加和脂肪生成率增加,而雌性脂肪细胞则表现出脂质生成减少。然而,将雌激素增加到生理水平以上也会减少女性的脂质合成,而增加男性的二氢睾酮则没有效果。脂肪组织中的胰岛素敏感性存在显着的性别差异,特别是在腹内储存库中,这是由性类固醇的生理水平调节的。尽管脂肪含量与男性相似或更高,但在女性脂肪细胞中观察到的对胰岛素和脂肪生成的敏感性增加可能是其胰岛素抵抗和糖尿病风险水平较低的原因。
To investigate how insulin sensitivity and glucose metabolism differ in adipocytes between different fat depots of male and female mice and how sex steroids contribute to these differences. Adipocytes from intra-abdominal/perigonadal (PG) and subcutaneous (SC) adipose tissue from normal, castrated, or steroid-implanted animals were isolated and analyzed for differences in insulin sensitivity and glucose metabolism. Adipocytes from both PG and SC depots of females have increased lipogenic rates compared with those from males. In females, intra-abdominal PG adipocytes are more insulin-sensitive than SC adipocytes and more insulin-sensitive than male adipocytes from either depot. When stimulated by low physiological concentrations of insulin, female PG adipocytes show a robust increase in Akt and extracellular signal–related kinase (ERK) phosphorylation and lipogenesis, whereas male adipocytes show activation only at higher insulin concentrations. Adipocytes from females have higher mRNA/protein levels of several genes involved in glucose and lipid metabolism. After castration, adipocytes of male mice showed increased insulin sensitivity and increased lipogenic rates, whereas adipocytes of females demonstrate decreased lipid production. Increasing estrogen above physiological levels, however, also reduced lipid synthesis in females, whereas increasing dihydrotestosterone in males had no effect. There are major sex differences in insulin sensitivity in adipose tissue, particularly in the intra-abdominal depot, that are regulated by physiological levels of sex steroids. The increased sensitivity to insulin and lipogenesis observed in adipocytes from females may account for their lower level of insulin resistance and diabetes risk despite similar or higher fat content than in males.
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