Scholars Webinar on: The Role of New Technologies

Drug Discovery, Development and Lead Optimization

THEME: "Experimental Challenges in Studies of Drug Discovery, Development and Lead Optimization"

img2 24-25 Mar 2021
img2 Webinar | Online | 11:00-17:00 GMT
Sanjay K Banerjee

Sanjay K Banerjee

National Institute of Pharmaceutical Research and Education, India

Title: A potential target for diabetic cardiomyopathy


Biography

Sanjay Kumar Banerjee is an Associate Professor and In-Charge at National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India. He completed, his PhD in Pharmacology from All India Institute of Medical Sciences, India. His research goal is to identifying and validating novel targets and therapeutic intervention for cardiovascular and metabolic disorders. His laboratory is mostly interested to understand molecular mechanisms of insulin resistance and cardiac complication in diabetes, and identify nutritional agents/natural products to reduce the disease progression. Overall goal is to bridge the gap between observations in the basic research laboratory and the clinical bedside. Sanjay K Banerjee studies will be an integral part in ‘‘translating’’ new discoveries into therapeutic initiatives.

Abstract

Several targets are being explored to reduce cardiac disorder in diabetes. Sirtuins, a group of deacetylases, are potential targets that can regulate cellular metabolism, oxidative stress, and mitochondrial health. Data showed that sirtuins, specially Sirt1 and Sirt3 activation can prevent or reverse the progression of several chronic metabolic diseases through the regulation of multiple histone and non-histone proteins. In the present study, we aimed to evaluate the effect of Sirt1, Sirt3 and combined activation in high fructose diet-induced insulin resistance rat heart and assessed the cardiac function focusing on mitochondrial health and function. We administered the Sirt1 activator; SRT1720 (5mg/kg, i.p.), Sirt3 activator; Oroxylin-A (10 mg/kg i.p.) and the combination; SRT1720+Oroxylin-A (5mg/kg and 10 mg/kg i.p.) daily from 12th week to 2oth weeks of study. We observed significant perturbations of most of the cardiac structural and functional parameters in high fructose diet-fed animals. Administration of SRT1720 and Oroxylin-A improved perturbed cardiac structural and functional parameters by decreasing insulin resistance, oxidative stress, and improving mitochondrial function by enhancing mitochondrial biogenesis, OXPHOS expression and activity in high fructose diet-induced insulin-resistant rats. However, we could not observe the synergistic effect of SRT1720 and Oroxylin-A combination. Similar to in-vivo study, perturbed mitochondrial function and oxidative stress observed in insulin resistant H9c2 cells were improved after activation of Sirt1 and Sirt3. We observed that Sirt1 activation enhances Sirt3 expression and mitochondrial biogenesis, and the opposite effects were observed after Sirt1 inhibition in cardiomyoblast cells. Taken together our results conclude that activation of Sirt1 alone could be a potential therapeutic target for diabetes-associated cardiac complications.