The absence of female sex hormones, as well as testosterone treatment of oophorectomized (OVX) female rats has been demonstrated to result in decreased whole-body insulin-mediated glucose uptake. The cellular mechanism behind this insulin resistance and the role of low levels of female sex hormones as a risk factor for development of peripheral insulin resistance are not yet fully clarified. We assessed the protein expression of GLUT4 and glycogen synthase, as well as insulin-induced translocation of GLUT4 to the plasma membrane, in soleus skeletal muscle from control rats, OVX rats, and OVX rats treated for 8 weeks with testosterone (OVX + T). Whole-body insulin-mediated glucose uptake assessed by the hyperinsulinemic-euglycemic clamp procedure was 25% lower in OVX rats (P < 0.001) and addition of testosterone treatment further decreased insulin-mediated glucose uptake in OVX + T rats by 48% (P < 0.001) compared with controls. GLUT4 protein expression in soleus muscles was unaltered in the OVX and OVX + T rats compared with controls. Insulin induced a 3.7-fold increase (P < 0.05) in the plasma membrane content of GLUT4 in soleus muscle from control rats, whereas plasma membrane content of GLUT4 in soleus muscle from OVX or OVX + T rats was unaltered in response to insulin. Glycogen synthase protein expression in muscle homogenates was decreased by 25% in the OVX group (P < 0.05) and by 37% in the OVX + T group (P < 0.05) when compared with the control group. Insulin receptor and tyrosine kinase activities in the basal and insulin-stimulated states did not differ between the OVX and OVX + T rats. In conclusion, the absence of female sex hormones appears to decrease insulin-mediated whole-body glucose uptake via an impaired insulin-stimulated translocation of GLUT4 to the plasma membrane and by decreased protein expression of glycogen synthase. Testosterone treatment further impairs whole-body insulin-mediated glucose uptake, presumably by additional impairment of glycogen synthase expression.
Mechanisms Behind Insulin Resistance in Rat Skeletal Muscle After Oophorectomy and Additional Testosterone Treatment
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Jorge Rincon, Agneta Holmäng, Erica Odegaard Wahlström, Peter Lönnroth, Per Björntorp, Juleen R Zierath, Harriet Wallberg-Henriksson; Mechanisms Behind Insulin Resistance in Rat Skeletal Muscle After Oophorectomy and Additional Testosterone Treatment. Diabetes 1 May 1996; 45 (5): 615–621. https://doi.org/10.2337/diab.45.5.615
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