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Sex steroids influence glucose oxidation through modulation of insulin receptor expression and IRS-1 serine phosphorylation in target tissues of adult male rat

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Abstract

Skeletal muscle, liver, and adipose tissue are major insulin responsive target organs that also express androgen receptor. Testosterone (T) plays a role in maintaining normal insulin sensitivity in men but its effects on insulin target tissues are not fully understood. Our previous study showed that orchidectomy impairs glucose oxidation through decreased insulin receptor (IR) mRNA expression in skeletal muscles, liver, and adipose tissue of male rat. Furthermore, T replacement restored IR mRNA expression in skeletal muscles and liver, but did not have any effect in adipose tissue. In the present study, orchidectomy decreased IR mRNA and protein levels in muscle, liver, and adipose tissue. Treatment with a combination of T plus estradiol (E) was necessary to restore the IR mRNA and protein to control levels in adipose tissue. T or E treatment alone had no effect on IR mRNA levels in adipose tissue. T alone also had no effect on the IR protein, whereas E alone had a stimulatory effect. In comparison, in muscle and liver, T or T plus E restored the IR mRNA and protein to control levels. In muscle and liver, E alone had no effect on IR mRNA expression but restored the IR protein. In addition, orchidectomy was seen to have a stimulatory effect on IRS-1 Serine636/639 phosphorylation in the three tissues studied. Following T, E or combined supplementation to castrated rats, the pattern of IRS-1 serine phosphorylation was restored to normal control levels. Furthermore, orchidectomy decreased serum insulin and glucose oxidation in all three tissues, and this was restored by T and its combination with E replacement, whereas E alone had no effect. It is concluded from the present study that sex steroid deficiency induces impaired glucose oxidation in insulin responsive tissues, which is mediated through reduced IR expression, and increased IRS-1 serine phosphorylation.

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Acknowledgments

Financial assistance from the Indian Council of Medical Research (ICMR), New Delhi in the form of Senior Research Fellowship (SRF) to T. Muthusamy (Award No. 3/1/2/15/05-RHN dated 9-8-2005), DST-FIST, UGC-SAP-DRS-II and UGC-ASIST programmes are gratefully acknowledged.

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  1. Thirupathi Muthusamy

    Present address: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA

Authors and Affiliations

  1. Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600 113, Tamil Nadu, India

    Thirupathi Muthusamy, Chinnapaiyan Srinivasan & Karundevi Balasubramanian

  2. Department of Obstetrics and Gynaecology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Palaniappan Murugesan

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Correspondence to Karundevi Balasubramanian.

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Muthusamy, T., Murugesan, P., Srinivasan, C. et al. Sex steroids influence glucose oxidation through modulation of insulin receptor expression and IRS-1 serine phosphorylation in target tissues of adult male rat. Mol Cell Biochem 352, 35–45 (2011). https://doi.org/10.1007/s11010-011-0737-1

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