Curcumin protects islet cells from glucolipotoxicity by inhibiting oxidative stress and NADPH oxidase activity bothin vitroandin vivo

Abstract

Curcumin possesses medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2 DM). It has been proposed that pancreatic beta cell dysfunction in T2 DM is promoted by oxidative stress caused by NADPH oxidase over-activity. The aim of the present study was to evaluate the efficacy of curcumin as a protective agent against high glucose/palmitate (HP)-induced islet cell damage and in streptozotocin (STZ)induced DM rats. INS-1 cells were exposed to HP with or without curcumin. Cell proliferation, islet cell morphological changes, reactive oxygen species production, superoxide dismutase and catalase activity, insulin levels, NADPH oxidase subunit expression, and the expression of apoptotic factors by INS-1 cells were observed. Our results show that curcumin can effectively inhibit the impairment of cell proliferation and activated oxidative stress, increase insulin levels, and reduce the high expression of NADPH oxidase subunits and apoptotic factors induced by HP in INS-1 cells. The STZ-induced DM rat model was also used to determine whether curcumin can protect islets in vivo. Our results show that curcumin significantly reduced pathological damage and increased insulin levels of islets in STZ-induced DM rats. Curcumin also successfully inhibited the high expression of NADPH oxidase subunits and apoptotic factors in STZ-induced DM rats. These results suggest that curcumin is able to attenuate HP-induced oxidative stress in islet cells and protect these cells from apoptosis by modulating the NADPH pathway. In view of its efficiency, curcumin has potential for translation applications in protecting islets from glucolipotoxicity.

Therapeutic potential of curcumin in diabetic retinopathy (Review)

“…The results of that study revealed that curcumin effectively inhibited the proliferation-induced damage and oxidative stress caused by high glucose in INS-1 cells, increased the insulin level, and reduced the expression of NADPH oxidase subunits and apoptotic factors. These results also suggested that curcumin alleviated high-glucose/palmitate-induced oxidative stress in islet cells by regulating the NADPH pathway and protected islet cells from apoptosis ( 34 ). Xia et al found that following curcumin administration, the activity of rat insulinoma RIN-m5F β-cells increased, the apoptotic rate of the cells decreased and the cells were protected ( 35 ).…”

“…Curcumin also plays an important protective role in cells under high-glucose conditions in in vitro experiments ( 34 , 35 ). In a study that exposed insulin (INS)-1 cells to high glucose with or without curcumin, the proliferation of INS-1 cells, the morphological changes of islet cells, the production of reactive oxygen species (ROS) as well as the activities of superoxide dismutase and catalase, insulin levels, the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, and the expression of apoptotic factors were observed ( 34 ). The results of that study revealed that curcumin effectively inhibited the proliferation-induced damage and oxidative stress caused by high glucose in INS-1 cells, increased the insulin level, and reduced the expression of NADPH oxidase subunits and apoptotic factors.…”

Renal microvascular damaged in diabetes mellitus with hyperlipidemia through the regulation of MAMs by PACS2 in endothelial cell

“…As previous studies have showed, HGHF can trigger unfolded protein response and cellular inflammation, leading to decreased insulin biosynthesis, impaired insulin secretion, or cell death [27,28]. And lymphatic vessel integrity dysfunction in mice models of obesity and type 2 diabetes [29].…”

Bilirubin Protects Transplanted Islets by Targeting Ferroptosis

“…During the islet collection, preservation, and transplantation, isolated islets always suffered extensive oxidative stress that significantly compromised the islet survival and function. It has been acknowledged that strategies that target islet redox signaling could potentially protect the islets from oxidative stress-induced damages (Li et al, 2019;Zhu et al, 2019). Ferroptosis, a form of programmed death, is characterized by the intensive oxidative stress and the involvement of iron.…”

“…Erastin could inhibit cystine uptake by interfering xCT transporters, which reduced the intracellular GSH biosynthesis and induced ferroptosis (Park and Chung, 2019). More importantly, the direct addition of over-load iron, FAC, has also been identified as an effective ferroptosis inducing approach (Li et al, 2019). It is viable to increase islet survival and function by reducing oxidative stress (Yao et al, 2019b).…”