Exogenous thyroxine improves glucose intolerance in insulin-resistant rats

Abstract

Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential gluco-regulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n=8): 1) lean, Long Evans Tokushima Otsuka (LETO), 2) obese, Otsuka Long Evans Tokushima Fatty (OLETF), and 3) OLETF + T4 (8.0 μg/100g BM/d × 5wks). T4 attenuated glucose intolerance by 15 % and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle GLUT4 mRNA expression. T4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (MCT10), deiodinase type (DI2), sirtuin 1 (SIRT1), and uncoupling protein 2 (UCP2) by 1.8-, 2.2-, 2.7-, and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to up regulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.

Molecular Mechanisms and Signaling Pathways Involved in Sertoli Cell Proliferation

“…SIRT1 activation also decreased c-Myc transcriptional activity (189). Remarkably, TH regulate SIRT1 expression and activity in different experimental models (190–192). SIRT1 activation might also be a molecular mechanism utilized by TH operating in immature Sertoli cells at the time of cessation of proliferation and terminal maturation of this cell type aimed to sustain spermatogenesis.…”

Partial Body Mass Recovery After Caloric Restriction Abolishes Improved Glucose Tolerance in Obese, Insulin Resistant Rats

“…Systolic blood pressure (SBP) was consistently measured in triplicate in conscious rats by tail-cuff plethysmography (BP-98A; Softron Co., Tokyo, Japan) (n = 6/group) as previously described (26,30,31). Rats were acclimated to the tube restraints prior to measurements.…”

The expression of sirtuins, superoxide dismutase, and lipid peroxidation status in peripheral blood from patients with diabetes and hypothyroidism

“…The THs T3 and T4 play key roles in regulating hepatic lipid, cholesterol, and glucose metabolism [22, 23]. Administration of T4 medication has been shown to activate T3, which in turn upregulates the important factors (e.g., SIRT1) that are involved in glucose homeostasis [24]. Furthermore, HT has been shown to be accompanied by oxidative stress [25, 26].…”