Stigmasterol prevents glucolipotoxicity induced defects in glucose-stimulated insulin secretion

Abstract

Type 2 diabetes results from defects in both insulin sensitivity and insulin secretion. Elevated cholesterol content within pancreatic β-cells has been shown to reduce β-cell function and increase β-cell apoptosis. Hyperglycemia and dyslipidemia contribute to glucolipotoxicity that leads to type 2 diabetes. Here we examined the capacity of glucolipotoxicity to induce free cholesterol accumulation in human pancreatic islets and the INS-1 insulinoma cell line. Glucolipotoxicity treatment increased free cholesterol in β-cells, which was accompanied by increased reactive oxygen species (ROS) production and decreased insulin secretion. Addition of AAPH, a free radical generator, was able to increase filipin staining indicating a link between ROS production and increased cholesterol in β-cells. We also showed the ability of stigmasterol, a common food-derived phytosterol with anti-atherosclerotic potential, to prevent the increase in both free cholesterol and ROS levels induced by glucolipotoxicity in INS-1 cells. Stigmasterol addition also inhibited early apoptosis, increased total insulin, promoted actin reorganization, and improved insulin secretion in cells exposed to glucolipotoxicity. Overall, these data indicate cholesterol accumulation as an underlying mechanism for glucolipotoxicity-induced defects in insulin secretion and stigmasterol treatment as a potential strategy to protect β-cell function during diabetes progression.

Microalgal carotenoids and phytosterols regulate biochemical mechanisms involved in human health and disease prevention

“…In human pancreatic islet and in the INS-1 insulinoma cell line, the use of stigmasterol prevents the increase of both cholesterol and ROS levels induced by glucolipotoxicity. In this study, stigmasterol has been shown to decrease free cholesterol levels resulting from glucolipotoxicity, with a real potential to protect pancreatic cells during diabetes progression [96].…”

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

“…The authors in question showed that the effect of this compound on antioxidant enzymes was mediated by the oestrogen/phosphatidylinositol 3-kinase pathway [ 97 ]. Meanwhile, studies performed on INS-1 insulinoma cells and human islets have shown that stigmasterol treatment can prevent β-cell dysfunction induced by glucolipotoxicity, an effect that was associated with decreased insulin secretion and increased ROS production [ 98 ].…”

Halophytic Grasses, a New Source of Nutraceuticals? A Review on Their Secondary Metabolites and Biological Activities

“…Stigmasterol ( 201 ), present in A. donax , C. ciliaris and D. bipinnata proved its value as an antiasthmatic agent, with suppressive effects on essential features of allergen-induced asthma (dietary administered in guinea pigs, 10, 50, 100 mg/kg) [122]. This compound also has the ability to protect pancreatic β-cells from glucotoxicity during diabetes progression through inhibition of early apoptosis, increasing total insulin and promoting insulin secretion [123].…”