Life Sciences & Biotechnology
Title : | Modulation of pancreatic beta cells by reactive oxygen and nitrogen species during dyslipidemia using NOS2KO and C57Bl/6 mice. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Priya Pathak, Amity University, Noida, Uttar Pradesh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | ppathak@lko.amity.edu |
Equipments : | "ECL detection kit (Amersham)
Laboratory Oven-AX (Carbolite- Zero)
NanoDrop™ 2000/2000c Spectrophotometers (ThermoFischer scientific)" |
Details
Executive Summary : | Insulin resistance (IR) and type II diabetes often linked with obesity and dyslipidemia, is defined as reduction in the ability to clear glucose load from the circulation in response to insulin. IR in LFD fed 8-week-old NOS2KO mice was reported from our lab(Babu Nageswararao Kanuri et al., 2017). Further we also reported incidence of IR in breeding diet fed adult NOS2KO mice which was partially reversed in presence of nitrite supplementation(Aggarwal et al., n.d.). IR, and the compensatory hyperinsulinemia, has been linked to glucose intolerance, diabetes, dyslipidemia, endothelial dysfunction etc (Cohn et al., 2001). Surprisingly we did not observe any vascular dysfunction in the NOS2KO mice fed on breeding, LFD or HFD diets(Pathak et al., 2019). Dyslipidemia was seen in NOS2KO mice from 8 week onwards, which was affirmed by increase in both serum and hepatic lipid levels. Muscle lipids were also increased at the later time points(B.N. Kanuri et al., 2018). Role of pancreatic β cells in dyslipidemia induced IR is very prevalent(Cerf, 2013). Pancreatic β cells initially compensate for the IR associated with obesity by upregulating the secretion of insulin. The β cell failure and diabetes that follow this period of β cell compensation may result from inadequate expansion of β cell mass or failure of the existing β cell mass to respond to glucose(Mezza et al., 2019). However, the association of pancreatic β cells with oxidative stress has not been explored much. Thus the present study will demonstrate the underlying mechanisms and modulations occurring in the pancreatic beta cells in NOS2KO mice. The following study will also deal with the age dependent changes occurring in pancreatic β cells in NOSKO mice. Keywords (max 6): Pancreas, NOS2, IR, human pancreatic cell line. Objectives of project (max 1500 characters): 1. Assess the status of IR in pancreas and comparison of glucose and lipid metabolism in the metabolic organs (skeletal muscle, liver and adipose tissue) of C57BL/6 and NOS2KO mice under normal and dyslipidemic condition. 2. Identify the novel redox regulated mechanisms involved in the functioning of pancreatic β cells of C57BL/6 and NOS2KO mice under normal and dyslipidemic condition. Further confirmation of results in human pancreatic cell line (EndoC-βH1) at different treatment levels. |
Total Budget (INR): | 29,47,901 |
Organizations involved