Endocrine Abstracts (2017) 49 EP636 | DOI: 10.1530/endoabs.49.EP636

Differential pattern of insulin signaling in adipose tissue and skeletal muscle in adult female sheep exposed prenatally to testosterone

Daniel Sandoval1, Mónica P Recabarren1, Albert Carrasco1, Teresa Sir-Petermann2 & Sergio E Recabarren1


1Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Medicine, University of Concepcion, Chillan, Region BioBio, Chile; 2Laboratory of Endocrinology and Metabolism, Western School of Medicine, Universidad de Chile, Santiago, Chile.


Insulin resistance is defined as the incapacity of insulin to increase glucose uptake by peripheral tissues (skeletal muscle and adipose tissue principally). This phenomenon is present in different animal models for PCOS by prenatal exposure to androgens. In the PCOS condition, the metabolic pathway of insulin activity is defective in skeletal muscle and adipocyte whereas the activation of steroidogenesis is maintained. The decreased insulin stimulated glucose uptake is due to impaired signaling and multiple downstream intracellular defects including impaired glucose transport and glucose metabolism. Previous results from our laboratory have demonstrated that female sheep born to mothers receiving testosterone during part of their pregnancy exhibit features from early postnatal life until adulthood resembling those of PCOS women. In the present work, the programming effect of prenatal testosterone on the insulin signaling was explored in adult females born to testosterone treated mothers (testosterone-females), and born to untreated mothers (C-females). Our aim was to define if prenatal exposure to testosterone affects insulin signaling in adipose tissue and skeletal muscle. Adults females (38 weeks of age) were sacrificed and samples of skeletal muscle (Gluteus superficialis) and adipose tissue (visceral) were collected. The qPCR assays were performed to analyze gene expression of IR, IRS-1, IRS-2, PI3K, Akt, PKC, GLUT4 and β-actin. Expression pattern of insulin signaling were similar between groups with the exception that in skeletal muscle, IRS-2 showed higher expression in testosterone-females (P≤0.05) than C-females while on the contrary, the GLUT4 RNAm was lower in testosterone-females compared to C-females (P≤0.05). In the visceral adipose tissue, AKT transcript expression was higher in testosterone-females (P≤0.05) than C-females. Results show that prenatal exposure to testosterone affects the insulin signaling, suggesting a change in the type of oxidative metabolism in the muscle tissue and increase in adipogenesis.

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