Efficacy of Vanadyl Sulfate and Selenium Tetrachloride as Anti-Diabetic Agents against Hyperglycemia and Oxidative Stress Induced by Diabetes Mellitus in Male Rats

The use of metals in medicine has grown in popularity in clinical and commercial settings. In this study, the immune-protecting effects and the hypoglycemic and antioxidant activity of vanadyl sulfate (VOSO4) and/or selenium tetrachloride (Se) on oxidative injury, DNA damage, insulin resistance, and hyperglycemia were assessed. Fifty male albino rats were divided into five groups, and all treatments were administrated at 9:00 a.m. daily for 60 successive days: control, STZ (Streptozotocin; 50 mg/kg of STZ was given to 6 h fasted animals in a single dose, followed by confirmation of diabetic state occurrence after 72 h by blood glucose estimation at >280 mg/dl), STZ (Diabetic) plus administration of VOSO4 (15 mg/kg) for 60 days, STZ (Diabetic) plus administration of selenium tetrachloride (0.87 mg/Kg), and STZ plus VOSO4 and, after 1/2 h, administration of selenium tetrachloride at the above doses. The test subjects’ blood glucose, insulin hormone, HbA1C, C-peptide, antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, myeloperoxidase, and xanthine oxidase), markers of lipid peroxidation (MDA), and histological sections of pancreatic tissues were evaluated, and a comet assay was performed. Histological sections in pancreas tissues were treated as indicators of both VOSO4 and selenium tetrachloride efficacy, either alone or combined, for the alleviation of STZ toxicity. The genotoxicity of diabetes mellitus was assessed, and the possible therapeutic roles of VOSO4 or selenium tetrachloride, or both, on antioxidant enzymes were studied. The findings show that the administration of VOSO4 with selenium tetrachloride reduced oxidative stress to normal levels, lowered blood glucose levels, and elevated insulin hormone. Additionally, VOSO4 with selenium tetrachloride had a synergistic effect and significantly decreased pancreatic genotoxicity. The data clearly show that both VOSO4 and selenium tetrachloride inhibit pancreatic and DNA injury and improve the oxidative state in male rats, suggesting that the use of VOSO4 with selenium tetrachloride is a promising synergistic potential ameliorative agent in the diabetic animal model.

Naturally Acquired Lactic Acid Bacteria from Fermented Cassava Improves Nutrient and Anti-dysbiosis Activity of Soy Tempeh

Introduction: Gut microbiota dysbiosis indicated by increased gram-negative bacteria and reduced Firmicutes-producing short chain fatty acids bacteria has been linked with impairment in glucose metabolism. Tempeh is traditional fermented soy food that can stimulate the growth of beneficial bacteria. In Indonesia, some tempeh was produced by adding acidifier that contains lactic acid bacteria. This process may impact the nutrient and anti-dysbiosis activity of tempeh. Objectives: To evaluate the impact of acidifier on nutrient and gut microbiota profile of diabetic animal model. Method: Modified tempeh was made by addition of water extract of fermented cassava. Standard and modified tempeh were subjected to proximate analysis and dietary fibre. Diabetic animals were received standard tempeh or modified tempeh diet replacing 15% and 30% of protein in the diet for 4 weeks of intervention. At the end of experiment, caecal content was collected. Short chain fatty acids and microbiota composition were analysed using 16s rDNA next generation sequencing (NGS). Result: There is significant different (p<0.05) on fat, protein, water and dietary fibre content between regular soy tempeh and modified tempeh. There is significant different (p<0.05) on serum glucose and short chain fatty acid composition among group. Diabetic animal has low ratio of Firmicutes/Bacteroidetes. Supplementation of both tempeh increased bacterial diversity, Firmicutes /Bacteroidetes ratio and short chain fatty acids producing bacteria. Conclusion: Addition of naturally occurred lactic acid bacteria from fermented cassava during tempeh processing improved both nutrient and microbiota composition in the gut of diabetes mellitus.

Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy

Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments.

Anti-diabetic Activity of Buchanania lanceolata Wight Extracts in Streptozocin persuade Diabetic Animal Model

Diabetes mellitus is a well-established metabolic syndrome that originates from a complete or virtual requirement of insulin and low insulin action, which leads to hyperglycemia and malformation in the regulation of lipids, proteins, and carbohydrates. Micro and macrovascular difficulties are mainly developed in diabetic patients when compared with normal individuals. The plant variety selected for this study was Buchanania lanceolata Wight (B. lanceolata), which comes under the family of Anacardiaceae, which was originated in India and Myanmar. In the current research, an aqueous extract of B. lanceolata was isolated from the plant barks. Glucose uptake was carried out by using L6 myoblast cell lines, and the results showed an improved glucose uptake in vitro by the aqueous extract of bark of B. lanceolata. Moreover, it was also studied for acute dose oral toxicity and anti-diabetic studies in Wistar albino rats. The aqueous extract did not demonstrate any toxic conditions or mortality at single dose feeding of 2000 mg/kg/p.o and was examined for 15 days. It was also found out the variations in glucose level, hematology parameters, lipid level, and biochemical factors of both control and treated animals. Currently, the natural drug gained attention among researchers because of the problems developed by the allopathic remedial representative. The examination of anti-diabetic agents of an herbal source that are used in folk medicine is thus of huge significance. Management of diabetes with artificial medicines is an expensive and high probability for side effects. As a result, it is necessary to develop plant-based medicines for diabetes. B. lanceolata is a promising herbal drug for diabetic treatment not only in Ayurveda but also in other folk medicine.

Functional and Structural Changes in the Corticospinal Tract of Streptozotocin-Induced Diabetic Rats

This study aimed to reveal functional and morphological changes in the corticospinal tract, a pathway shown to be susceptible to diabetes. Type 1 diabetes was induced in 13-week-old male Wistar rats administered streptozotocin. Twenty-three weeks after streptozotocin injection, diabetic animals and age-matched control animals were used to demonstrate the conduction velocity of the corticospinal tract. Other animals were used for morphometric analyses of the base of the dorsal funiculus of the corticospinal tract in the spinal cord using both optical and electron microscopy. The conduction velocity of the corticospinal tract decreased in the lumbar spinal cord in the diabetic animal, although it did not decrease in the cervical spinal cord. Furthermore, atrophy of the fibers of the base of the dorsal funiculus was observed along their entire length, with an increase in the g-ratio in the lumbar spinal cord in the diabetic animal. This study indicates that the corticospinal tract fibers projecting to the lumbar spinal cord experience a decrease in conduction velocity at the lumbar spinal cord of these axons in diabetic animals, likely caused by a combination of axonal atrophy and an increased g-ratio due to thinning of the myelin sheath.

VDR/Atg3 Axis Regulates Slit Diaphragm to Tight Junction Transition via p62-mediated Autophagy Pathway in Diabetic Nephropathy

Foot process effacement is an important feature of early diabetic nephropathy (DN) which is closely related to the development of albuminuria. Under certain nephrotic conditions, the integrity and function of the glomerular slit diaphragm (SD) structure were impaired and replaced by the tight junction (TJ) structure, resulting in so-called SD-TJ transition, which could partially explain the effacement of foot processes at the molecular level. However, the mechanism underlying the SD-TJ transition has not been described in DN. Here, we demonstrated that impaired autophagic flux blocked p62 mediated degradation of ZO-1 (TJ protein) and promoted podocytes injury via activation of caspase 3 and caspase 8. Interestingly, the expression of VDR in podocytes was decreased under diabetic condition which impaired autophagic flux through down-regulating Atg3. Of note, we also found that VDR abundance was negatively associated with impaired autophagic flux and SD-TJ transition in the glomeruli from human renal biopsy samples with DN. Furthermore, VDR activation improved autophagic flux and attenuated SD-TJ transition in the glomeruli of diabetic animal models. In conclusion, our data provided the novel insight that VDR/Atg3 axis deficiency resulted in SD-TJ transition and foot processes effacement via blocking p62-mediated autophagy pathway in DN.<br>

VDR/Atg3 Axis Regulates Slit Diaphragm to Tight Junction Transition via p62-mediated Autophagy Pathway in Diabetic Nephropathy

Foot process effacement is an important feature of early diabetic nephropathy (DN) which is closely related to the development of albuminuria. Under certain nephrotic conditions, the integrity and function of the glomerular slit diaphragm (SD) structure were impaired and replaced by the tight junction (TJ) structure, resulting in so-called SD-TJ transition, which could partially explain the effacement of foot processes at the molecular level. However, the mechanism underlying the SD-TJ transition has not been described in DN. Here, we demonstrated that impaired autophagic flux blocked p62 mediated degradation of ZO-1 (TJ protein) and promoted podocytes injury via activation of caspase 3 and caspase 8. Interestingly, the expression of VDR in podocytes was decreased under diabetic condition which impaired autophagic flux through down-regulating Atg3. Of note, we also found that VDR abundance was negatively associated with impaired autophagic flux and SD-TJ transition in the glomeruli from human renal biopsy samples with DN. Furthermore, VDR activation improved autophagic flux and attenuated SD-TJ transition in the glomeruli of diabetic animal models. In conclusion, our data provided the novel insight that VDR/Atg3 axis deficiency resulted in SD-TJ transition and foot processes effacement via blocking p62-mediated autophagy pathway in DN.<br>