Pratibha V. Nerurkar
Scientific Tracks Abstracts: J Diabetes Metab
Diabetes is the fi ft h deadliest disease in the United States, accounting for 17,000 deaths per year. Disruption of the interface between infl ammatory and stress pathways, specifi cally ER stress, is central to the pathogenesis of obesity, hepatic insulin resistance and type 2 diabetes (T2D). Accumulation of unfolded and misfolded proteins in ER activates the unfolded protein response (UPR), leading to increased expression of molecular chaperone Grp78/BiP and ATF4/CREB-2, an activating transcription factor. In addition, GADD153/CHOP, a growth arrest- and highly stress-inducible gene sensitizes cells to ER stress through enhancing production of reactive oxygen species that can promote infl ammation. Ayurvedic medicine, Momordica charantia (bitter melon, BM) is traditionally used in the management of diabetes and its complications. Th e aim of this study was to examine the eff ects of BM on hepatic ER stress and systemic infl ammation in mice fed high-fat diet (HFD). Our studies indicate that HFD signifi cantly elevated Grp78, ATF4 and GADD153 protein levels, while BM normalized levels of hepatic ER stress proteins in mice fed HFD with BM. Furthermore, BM attenuated systemic infl ammation by reducing secretion of plasma proinfl ammatory cytokines, INFγ, IL-17, TNFα, exotaxin-2, lymphotactin and IL-1b in mice fed HFD with BM. Interestingly, BM upregulated specifi c Th 2 cytokines IL-5, IL-10 and IL-13, which have been demonstrated to protect obesity-associated infl ammation. Th ese data indicate a role for dietary therapies in reducing HFD-associated hepatic ER stress and infl ammation. [Grants: NCMHD (P20MD000173-06), NCCAM (R21AT003719), RCMI, NCRR (5G12RR003061-23), NIH].
Dr. Pratibha V. Nerurkar obtained her Ph.D from Bombay University, India and completed her postdoctoral studies at National Cancer Institute/ National Institutes of Health (NCI/NIH). She leads the Laboratory of Metabolic Disorders and Alternative Medicine at College of tropical Agriculture, University of Hawaii. She has published more than 30 manuscripts in peer-reviewed journals.
