Effect of Telmisartan or Insulin on the Expression of Adiponectin and its Receptors in the Testis of Streptozotocin-Induced Diabetic Rats

Abstract

This study investigated the effect of insulin and telmisartan on the expression of adiponectin and its receptors, oxidative stress, and inflammatory cytokines in the testis of streptozotocin-induced diabetic rats. Male Wistar rats were randomly divided into control (C, n=8), diabetic (D, n=8), diabetic treated with insulin (DI, n=8), and diabetic treated with telmisartan (DT, n=8). Diabetic was induced by the peritoneal injection of a single dose of streptozotocin. Eight weeks later, bilateral testes were immediately removed after the rat was sacrificed. Epididymis was harvested to prepare sperm suspension. Plasma adiponectin, testicular interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA). The mRNA or protein expression of testicular adiponectin receptor 1 (adipoR1) and 2 (adipoR2), p22phox, transcription factor NF-E2 associated factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), AMPK-α, Akt, and eNOS was assayed by real-time fluorescence quantitative PCR or Western blot. There were significant pathological changes in the testes of diabetic rats. The levels of testicular weight, sperm number and motility, serum and testicular testosterone, plasma insulin and adiponectin, testicular adiponectin and its receptor 1, Nrf2, NQO1, HO-1, and phosphorylated-AMPK were significantly decreased in diabetic rats. The levels of blood glucose and lipids, and the levels of testicular p22phox, IL-6, TNF-α, phosphorylated-AKT, e-NOS, and nitric oxide (NO) were significantly increased in diabetic rats. These changes could be significantly reversed by insulin treatment. Similar results were observed with telmisartan treatment except for NQO1 mRNA and phosphorylated-AMPK. There was no significant difference in the expression of testicular adiponectin receptor 2 among 4 groups. The decreased adiponectin and its receptors, and the increased oxidative stress and inflammatory cytokines may play an important role in the testopathy of type 1 diabetic rats. Insulin and telmisartan may produce the protective effect on the testes of diabetic rats by upregulating the expression of adiponectin and its receptors and downregulating the level of oxidative stress and inflammatory cytokines.