Life Sciences & Biotechnology
Title : | Understanding the role of dietary flavonoids in regulation of GsK-3, GLUT4, human amylin (hA) aggregation and hA induced cytotoxicity in pancreatic β-islets: Experimental and in silico analysis |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Prof. Raju Nivarti Gacche, savitribai Phule Pune University, Maharashtra |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | rngacche@rediffmail.com |
Equipments : | Real-Time PCR system |
Details
Executive Summary : | India, known as the diabetic capital of the world, is home to over 80 million people affected by diabetes mellitus. Human amylin (hA) co-sectored with insulin is implicated in the pathogenesis of T2DM and has been targeted for developing novel antidiabetic agents. studies have shown that deposits of hA oligomeric aggregates induce cytotoxicity, apoptosis, and dysfunction of β-cells. Developing hA inhibitors, particularly from natural sources, is a key area of anti-diabetic research. Activated glycogen synthase kinase 3 (GsK-3) inactivates glycogen synthase by phosphorylation and arrests glucose deposition. Insulin can restore GsK-3 activity by regulating the PI3K/Akt signaling pathway. Over 40 different proteins are regulated by GsK3, governing various cellular signaling and processes. Inhibition of GsK-3 has been identified as an attractive target for effective diabetes management. GLUT4 are insulin-activated glucose transporters, and developing 'Dietary Activators for GLUT4 Expression' has attracted the research community and food & nutrition industry for engineering functional foods and nutraceuticals that fulfill energy requirements, reduce diabetes prevalence, and improve insulin sensitivity. Flavonoids, secondary metabolites of plants, are extensively investigated for their diverse biological activities. The proposed project aims to explore the structurally diverse panel of dietary flavonoids (DFs) as inhibitors of hA aggregation, understand their role in ameliorating hA aggregate-induced cytotoxicity in β-islets, and build a pharmacophore model of flavonoid scaffold for inhibition of hA and GsK-3. |
Total Budget (INR): | 50,04,338 |
Organizations involved