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- Title
Gender and Depot Differences in Adipocyte Insulin Sensitivity and the Sexual Dimorphism of Insulin Resistance.
- Authors
Macotela, Yazmin; Boucher, Jeremie; Tran, Thien T.; Gesta, Stephane; Kahn, C. R.
- Abstract
Obesity increases the risk for developing type 2 diabetes and metabolic syndrome. Surprisingly, however, despite having higher fat mass, women are more insulin sensitive than men, suggesting some gender dependent regulation of insulin sensitivity. Likewise female rodents are more likely to retain normal glucose tolerance compared to males when subjected to obesity or genetically induced insulin resistance. The objective of this study was to investigate how insulin sensitivity and glucose metabolism differ in adipocytes between male and female mice and how estrogen and testosterone may contribute to these differences. Adipocytes were isolated from intraabdominal/perigonadal (PG) and subcutaneous (SC) depots from male and female mice. In both depots, adipocytes from females had increased basal and insulin-stimulated lipogenic rates compared to those from males. Moreover, females adipocytes from the PG depot, but not the SQ depot, showed further increased insulin sensitivity, i.e. had a lower ED50, while in males this difference did not occur. Indeed, female perigonadal adipocytes stimulated with physiological concentrations of insulin showed a robust increase in AKT phosphorylation, whereas male adipocytes showed almost no activation at the same concentration. Quantitative PCR and western blotting demonstrated that females adipocytes had higher mRNA and protein levels of genes involved in glucose and lipid metabolism, including GLUT1, GLUT4, FAS and ACC, than males. In females, but not males, adipocytes from the PG depot also had higher expression levels than adipocytes from SC depots. After castration, adipocytes of male mice revealed increased insulin sensitivity and increased lipogenic rates, whereas female adipocytes had decreased insulin sensitivity and lipid production. Together, these results demonstrate major roles of sex steroids in the regulation of gender differences in insulin sensitivity in adipose tissue, especially in the intraabdominal depot, that can contribute to differences in diabetes risk in males and females at similar levels of body fat.
- Subjects
SEX factors in disease; INSULIN resistance; GLUCOSE; FAT cells; TYPE 2 diabetes; INSULIN; ESTROGEN; TESTOSTERONE
- Publication
Diabetes, 2007, Vol 56, pA338
- ISSN
0012-1797
- Publication type
Article