Abstract: Background: Testosterone facilitates various metabolic processes in the bones, muscles, bone marrow, brain and immune system. Testosterone deficiency may contribute to cardiovascular diseases, central obesity and metabolic dysfunction.
Aim: to investigate the effects of testosterone deficiency on blood glucose levels, insulin sensitivity, vitamin D, Homeostatic model assessment of insulin resistance (HOMA-IR), Homeostatic model assessment for beta function (HOMA-IR) and serum lipids in rat models of andropause. Methods, 48 male rats divided into 4 equal groups (n=12/group); a) Control (C) group. b) Orchiectomy (O) group underwent bilateral removal of the testicles. c) Orchiectomy and treated (O+T) group given daily IM testosterone replacement therapy for 7 days, d) Sham and treated (Sh+T) group in which sham operated rats were given the same daily dose of T as O+T group for 7 days. Results: we found that plasma glucose concentration increased significantly (P<0.001) in O group. This increase was corrected by testosterone injection in O+T group. In (Sh+T) group, there is a significant reduction in serum glucose (P<0.001). We also found that insulin level reduced significantly (P<0.001) in O group. This reduction in insulin level was corrected by testosterone. In (Sh+T) group, insulin level increased significantly. 25-OHVD3 was reduced significantly (P<0.05) in O group and increased significantly in O+T group. HOMA-IR level decreased significantly (P<0.001) and this reduction was corrected by Testosterone. HOMA-β reduced significantly (P<0.001) and this reduction was corrected by Testosterone in O+T group. In SH group, there is a marked increase in HOMA-β. We also found insignificant differences between the four groups in serum triglycerides. However, we found very highly significant differences in total cholesterol, LDL and VLDL between C group and O group and very highly significant differences between O+T group and Sh+T group in comparison with O group. We also found significant differences in serum HDL-c in (O) group in comparison with (C) group and between O+T and Sh+T groups in comparison with O group. In conclusion, we found
significant reduction in 25-OH(VD), Testosterone, Insulin, HOMA-IR and HOMA-B and significant increase in glucose serum levels in O group and these changes were corrected by Testosterone injection in O+T group. We also found insignificant differences between the four groups in serum triglycerides. However, we found highly significant differences in total cholesterol, LDL, HDL-c and VLDL between C group and O group and very highly significant differences between O+T group and Sh+T group in comparison with O group.  

Purpose

Understanding the pathogenesis and the molecular mechanisms of diabetic nephropathy (DN) helps its timely detection and prevention. The current work aims tomeasure serum sestrin 2 and betatrophin levels in healthy and type diabetic (T2DM)subjects with/or without diabetic nephropathy (DN) and also to test their correlation with serum neutrophil gelatinase associated lipocalin (sNGAL); indicator of DN.

Methods

This study included 96 subjects; 20 healthy (G1) and 76 T2DM [22 normoalbuminuric (G2), 35 microalbuminuric (G3) and 19 macroalbuminuric (G4)]. Serum sestrin 2, betatrophin and NGAL were measured by their corresponding kits.

Results

Significant low levels of serum sestrin 2 andhigh levels of serum betatrophin were found in T2DM group when compared to G1 (p = 0.002,p > 0.001, respectively) and this difference is manifested in G4 followed, in order, by G3, G2 then G1 (p= > 0.001 for both). Also, serum sestrin2 levels showed significant negative correlations with sNGAL in G1 (r = −0.497, p = 0.026), G2 (r = −0.784, p > 0.001), G3 (r = −0.894, p > 0.001) and G4 (r = −0.896, pp. > 0.001) while serum betatrophin levels showed significant positive correlations with sNGAL in G2 (r = 0.681, p > 0.001), G3 (r = 0.518, p > 0.001) and G4 (r = 0.727, p > 0.001).

Conclusion

Serum sestrin 2 levels decrease significantly while betatrophin levels increase significantly in T2DM patients with DN especially those with macroalbuminuria. These levels have significant effect strengths on the indicator of diabetic nephropathy; sNGAL which might indicate their valuable role in the timely detection and prevention of the development of DN.

Background: Oxidative stress, lipid profile and renal functions are well-known conventional risk factors for diabetes mellitus (DM). Metformin and gliclazide are popularly used monotherapy drugs for the treatment of DM. Aims: This study aims to assess the short-term treatment of single and dual therapy of glipizide/metformin on oxidative stress, glycemic control, serum lipid profiles and renal function in diabetic rats. Methods: DM was induced in rats with streptozotocin (STZ), then five different treatments were applied, including group I (untreated healthy control), group II (diabetic and untreated), group III (diabetic and treated with metformin), group IVI (diabetic and treated with glipizide) and group V (diabetic and treated with a combination of metformin and glipizide. Lipid peroxidation (LPO), nitric oxide (NO), total antioxidant capacity (TAC), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and urea were measured. Results: Compared to the untreated DM group, FBG and HbA1c were significantly reduced in the DM groups (p < 0.01) treated with metformin (159.7 mg/dL & 6.7%), glipizide (184.3 mg/dL & 7.3%) and dual therapy (118 mg/dL & 5.2%), respectively. Treatment with dual therapy and metformin significantly decreased LPO and NO levels but increased TAC in diabetic rats more than glipizide compared to untreated diabetic rats. Furthermore, metformin (19.8 mg/dL, p < 0.001), glipizide (22.7 mg/dL, p < 0.001), and dual therapy (25.7 mg/dL, p < 0.001) significantly decreased urea levels in the treated rats compared to untreated DM rats (32.2 mg/dL). Both drugs and their combination exhibited a substantial effect on total cholesterol, HDL, LDL and atherogenic index. Conclusions: These results suggest that the therapeutic benefits of metformin and glipizide are complementary. Metformin exhibited superior performance in improving glycemic control and decreasing oxidative stress, while glipizide was more effective against dyslipidemia. These findings could be helpful for the treatment of future vascular patients, antilipidemic medicines and antioxidant therapy to improve the quality of life.