Prenatal Testosterone Programming of Insulin Resistance in the Female Sheep

  • Muraly Puttabyatappa
  • Vasantha Padmanabhan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1043)


Insulin resistance, a common feature of metabolic disorders such as obesity, nonalcoholic fatty liver disease, metabolic syndrome, and polycystic ovary syndrome, is a risk factor for development of diabetes. Because sex hormones orchestrate the establishment of sex-specific behavioral, reproductive, and metabolic differences, a role for them in the developmental origin of insulin resistance is also to be expected. Female sheep exposed to male levels of testosterone during fetal life serve as an excellent translational model for delineating programming of insulin resistance. This chapter summarizes the ontogeny of insulin resistance, the tissue-specific changes in insulin sensitivity, and the various factors that are involved in the programming and maintenance of the insulin resistance in adult female sheep that were developmentally exposed to fetal male levels of testosterone during the sexual-differentiation window.


Testosterone Developmental Programming Insulin Resistance Adiponectin Oxidative Stress Inflammation Lipotoxicity Sheep 


Funding Support

This work was supported by NIH P01 HD44232.

Disclosure Statement

The authors have nothing to disclose.


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of MichiganAnn ArborUSA

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