Diabetic Neuropathy: Review on Molecular Mechanisms.

Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035. Consistent hyperglycemia leads to one of the most common comorbidities like Diabetic Peripheral Neuropathy (DPN). DPN is underlined with unpleasant sensory experience, such as tingling and burning sensation, hyperalgesia, numbness, etc. Globally, 50-60% of the diabetic population is suffering from such symptoms as microvascular complications. Consistent hyperglycemia during DM causes activation/inhibition of various pathways playing important role in the homeostasis of neurons and other cells. Disruption of these pathways results into apoptosis and mitochondrial dysfunctions, causing neuropathy. Among these, pathways like Polyol and PARP are some of the most intensively studied ones whereas those like Wnt pathway, Mitogen activated protein kinase (MAPK), mTOR pathway are comparatively newly discovered. Understanding of these pathways and their role in pathophysiology of DN underlines a few molecules of immense therapeutic value. The inhibitors or activators of these molecules can be of therapeutic importance in the management of DPN. This review, hence, focuses on these underlying molecular mechanisms intending to provide therapeutically effective molecular targets for the treatment of DPN.

Effect of Costus pictus per se and in combination with Metformin and Enalapril in streptozotocin induced diabetic nephropathy in rats.

Aim: The present study was designed to investigate the effect of methanolic extract of Costus pictus (MECP) per se and in combination with drugs (Metformin and Enalapril) used in clinical practice in streptozotocin (STZ) induced diabetic nephropathy (DN) in rats. Methods: Diabetes was induced in male Wistar rats by a single injection of STZ (50 mg/kg i.p.). After 28 days diabetic rats were divided into six groups. Two groups were treated with MECP (200 mg/kg p.o.), MECP (400 mg/kg p.o.) respectively; one group was treated with metformin (225 mg/kg), enalapril (3.2 mg/kg) combination; and two groups were treated with a combination of metformin, enalapril and MECP (200 mg/kg) and combination of metformin, enalapril and MECP (400 mg/kg) respectively. One group was kept as diabetic control. At the end of the study, body weight, kidney weight, and kidney hypertrophy index were evaluated. Biochemical and antioxidant parameters were evaluated. TGF-ß levels in serum were estimated. Histopathology of the kidney was also studied. Results: The combination therapy showed a significant increase in the body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in STZ induced diabetic nephropathy in rats. It also normalized the altered levels of serum and urine parameters. Histopathological evaluation revealed that combination therapy reduced the vacuolar degeneration of tubules. Conclusions: The results indicate that combination therapy of metformin, enalapril, and MECP has beneficial effects in management of diabetic nephropathy.

The effect of Madhumeha Kusumakar Rasa - an Ayurved medicine - in insulin resistance.

OBJECTIVES: Madhumeha Kusumakar Rasa (MKR) is an Ayurved formulation having a strong pharmacological base for diabetes management. This study aimed to validate MKR's efficacy in dexamethasone-induced insulin resistance (IR). METHODS: Albino Wistar rats were divided into four groups. Group 1 served as the normal control, Group 2 received dexamethasone 1.5 mg/kg (i.p.), Group 3 received dexamethasone and metformin 200 mg/kg (p.o.), and Group 4 received dexamethasone and MKR 236 mg/kg (p.o.). Animals were evaluated for serum glucose levels and glucose tolerance, serum insulin, Homeostatic model assessment of insulin resistance (HOMA-IR), Homeostatic model assessment of insulin sensitivity (HOMA-IS), fasting glucose to insulin ratio (FGIR), and lipid parameters. Pancreas, liver, and kidneys were evaluated for reduced Glutathione (GSH) and Malondialdehyde (MDA) levels. These tissues were also evaluated for histopathological changes. RESULTS: MKR showed significant improvement in serum glucose and glucose tolerance, serum insulin and HOMA-IR, HOMA-IS, and FGIR. It also showed a significant improvement in lipid parameters as compared to the dexamethasone-treated group. It prevented depletion of GSH levels and elevation in MDA levels. These effects were supported by histopathological analysis. CONCLUSIONS: MKR treatment significantly attenuated dexamethasone-induced IR. This study validates the mechanism of the anti-diabetic potential of MKR.