title: Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats.
abstract: The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.
authors.forename: Kahkashan
authors.initials: K
authors.lastname: Rashid
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India. Electronic address: parames@jcbose.ac.in.
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D016207:Cytokines; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495637:Nfe2l2 protein, rat; C495683:Slc2a2 protein, rat; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D003474:Curcumin
keywords: Antioxidant; Curcumin; Diabetes; ER/mitochondrial dependent and independent apoptosis; Inflammation; Oxidative and endoplasmic reticulum (ER) stress