Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function
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ABSTRACT:
SUBMITTER: Farnaz P
PROVIDER: S-EPMC10864770 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:This study was designed to (1) investigate the possible mechanisms through which diabetes-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) activation can affect male reproductive function; and (2) corroborate the interaction of previously established independent pathways. Male albino Wistar rats (14-weeks old) weighing 250-300 g received either a single intraperitoneal injection of streptozotocin (30 mg/kg or 60 mg/kg), represented as STZ30 or STZ60 respectively, or citrate buffer (control). Diabetes mellitus (DM) was confirmed if plasma glucose levels were ≥ 14 mmol/L after 1 week. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160 mg/kg body weight). The testes and epididymides were harvested. The testes were used for biochemical and Western blot analysis, while sperm was retrieved from the epididymis and analysed with computer-aided sperm analysis. The blood glucose levels of STZ60 animals were above the cut-off point and hence these animals were regarded as diabetic. Diabetic animals presented with a non-significant increase in AGE and RAGE expression. Diabetic animals showed a significant increase in the expression of cleaved caspase 3 compared to control (p < 0.001), and these animals also presented with an increase in the expression of JNK (p < 0.05), PARP (p = 0.059) and p38 MAPK (p = 0.1). Diabetic animals also displayed decreased catalase activity accompanied by a non-significant increase in malondialdehyde levels. Additionally, there was a significant decrease in the percentage of progressively motile spermatozoa (p < 0.05) in diabetic animals. This study has shed some light on the interplay between DM, AGE, RAGE and mitogen-activated protein kinase signalling in the testes of diabetic rats, which can result in altered sperm function and contribute to male infertility. However, more studies are needed to better understand this complicated process.
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Project description:Type I diabetes, though contributes to only 5-10% of total diabetes cases, is a rising concern in today's world. Our previous studies have shown that the absence of WDR13 in mouse results in pancreatic β-cell hyper-proliferation. Also, amelioration of the diabetic phenotype on introgression of Wdr13-null (Wdr13-/0) mutation in genetically diabetic mice (Leprdb/db) [type II diabetes] was observed. It was thus, interesting to see the role of WDR13 in streptozotocin-mediated diabetes in mice, a model for type I diabetes. Wdr13-/0 mice along with its wild type (Wdr13+/0 mice) littermates were administered streptozotocin intraperitoneally for 5 consecutive days. Blood glucose levels and body weights of these mice were monitored for subsequent 5 weeks and then they were sacrificed for physiological and histological analyses. Results showed that Wdr13-/0 mice exhibited higher serum insulin levels, better glucose clearance and significantly higher number of proliferating β-cells; reiterating the finding that absence of WDR13 helps in β-cell hyper-proliferation and recovery from diabetes; further underscoring WDR13 as a key target molecule for diabetes treatment/amelioration.
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Project description:Black ginseng, a new type of processed ginseng that has a unique ginsenoside profile, has been shown to display potent pharmacological activities in in vitro and in vivo models. Although red ginseng is considered beneficial for the prevention of diabetes, the relationship between black ginseng and diabetes is unknown. Therefore, this study was designed to evaluate the anti-diabetic potential of black ginseng extract (BGE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice, in comparison with red ginseng extract (RGE). HPLC analyses showed that BGE has a different ginsenoside composition to RGE; BGE contains Rg5 and compound k as the major ginsenosides. BGE at 200 mg/kg reduced hyperglycemia, increased the insulin/glucose ratio and improved islet architecture and β-cell function in STZ-treated mice. The inhibition of β-cell apoptosis by BGE was associated with suppression of the cytokine-induced nuclear factor-κB-mediated signaling pathway in the pancreas. Moreover, these anti-diabetic effects of BGE were more potent than those of RGE. Collectively, our data indicate that BGE, in part by suppressing cytokine-induced apoptotic signaling, protects β-cells from oxidative injury and counteracts diabetes in mice.
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Project description:ObjectiveNicotinamide rescues β-cell damage and diabetes in rodents, but a large-scale clinical trial failed to show the benefit of nicotinamide in the prevention of type 1 diabetes. Recent studies have shown that Sirt1 deacetylase, a putative protector of β-cells, is inhibited by nicotinamide. We investigated the effects of isonicotinamide, which is a derivative of nicotinamide and does not inhibit Sirt1, on streptozotocin (STZ)-induced diabetes in mice.Research design and methodsMale C57BL/6 mice were administered with three different doses of STZ (65, 75, and 100 mg/kg BW) alone or in combination with subsequent high-fat feeding. The mice were treated with isonicotinamide (250 mg/kg BW/day) or phosphate-buffered saline for 10 days. The effects of isonicotinamide on STZ-induced diabetes were assessed by blood glucose levels, glucose tolerance test, and immunohistochemistry.ResultsIsonicotinamide effectively prevented hyperglycemia induced by higher doses of STZ (75 and 100mg/kg BW) alone and low-dose STZ (65 mg/kg BW) followed by 6-week high-fat diet in mice. The protective effects of isonicotinamide were associated with decreased apoptosis of β-cells and reductions in both insulin content and insulin-positive area in the pancreas of STZ-administered mice. In addition, isonicotinamide inhibited STZ-induced apoptosis in cultured isolated islets.ConclusionsThese data clearly demonstrate that isonicotinamide exerts anti-diabetogenic effects by preventing β-cell damage after STZ administration. These findings warrant further investigations on the protective effects of isonicotinamide and related compounds against β-cell damage in diabetes.
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