The dysfunction of pancreatic β-cells plays a central role in the onset and progression of type 2 diabetes mellitus (T2DM). Insulin secretory defects in β-cells are characterized by a selective impairment of glucose stimulation, and a reduction in glucose-induced ATP production, which is essential for insulin secretion. High glucose metabolism for insulin secretion generates reactive oxygen species (ROS) in mitochondria. In addition, the expression of antioxidant enzymes is very low in β-cells. Therefore, β-cells are easily exposed to oxidative stress. In islet studies using a nonobese T2DM animal model that exhibits selective impairment of glucose-induced insulin secretion (GSIS), quenching ROS generated by glucose stimulation and accumulated under glucose toxicity can improve impaired GSIS. Acute ROS generation and toxicity cause glucose metabolism disorders through different molecular mechanisms. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor, is a master regulator of antioxidant defense and a potential therapeutic target in oxidative stress-related diseases, suggesting the possible involvement of Nrf2 in β-cell dysfunction caused by ROS. In this review, we describe the mechanisms of insulin secretory defects induced by oxidative stress in diabetic β-cells.

Long-term administration of Ipomoea batatas L. (white-skinned sweet potato, WSSP) has been reported to help manage type 2 diabetes mellitus (T2DM) in humans and animals; however, the mechanisms of blood glucose regulation by WSSP remain unclear. Therefore, we aimed to investigate the acute effects of WSSP on blood glucose homeostasis under normal conditions and the underlying mechanisms. Three fractions of WSSP (≤10, 10-50, and >50 kDa) were obtained via ultracentrifugation. Rats were subjected to an oral glucose tolerance test (OGTT) after a single administration of WSSP. The insulin tolerance test (ITT) and pyruvate tolerance test (PTT) were performed to evaluate insulin sensitivity and gluconeogenesis, respectively. Single WSSP administration markedly reduced blood glucose levels as revealed by the OGTT. Serum insulin levels were not increased by WSSP treatment. Blood glucose levels during ITT were significantly reduced due to WSSP treatment. WSSP treatment activated the phosphorylation of Akt, thereby activating insulin signaling in the skeletal muscles and liver. The ≤10 kDa fraction considerably reduced blood glucose levels per the OGTT and ITT. In contrast, gluconeogenesis in PTT and the expression of key enzymes in hepatocytes were suppressed by the >50 kDa fraction. This study demonstrated that WSSP acutely reduced postprandial blood glucose levels by improving insulin sensitivity in skeletal muscles in normal rats, which was attributed to constituents with a molecular weight of ≤10 kDa. Moreover, WSSP treatment suppressed gluconeogenesis in the liver, for which constituents of >50 kDa were responsible. Thus, WSSP can acutely regulate blood glucose homeostasis via multiple mechanisms. Since postprandial hyperglycemia leads to the onset of T2DM, WSSP, as a functional food, may possess potential active compounds that prevent T2DM.

Bitter melon (Momordica charantia L.) has been shown to have various health-promoting activities, including antidiabetic and hypoglycaemic effects. Improvement in insulin sensitivity and increase in glucose utilisation in peripheral tissues have been reported, but the effect on insulin secretion from pancreatic β-cells remains unclear. In this study, we investigated the effect of bitter melon fruit on insulin secretion from β-cells and the underlying mechanism. The green fruit of bitter melon was freeze-dried and extracted with methanol. The bitter melon fruit extract (BMFE) was fractionated using ethyl acetate (fraction A), n-butanol (fraction B) and water (fraction C). Insulin secretory capacity from INS-1 rat insulinoma cell line and rat pancreatic islets, as well as glucose tolerance in rats by oral glucose tolerance test (OGTT), was measured using BMFE and fractions. ATP production in β-cells was also examined. BMFE augmented insulin secretion from INS-1 cells in a dose-dependent manner. The significant augmentation of insulin secretion was independent of the glucose dose. Fraction A (i.e. hydrophobic fraction), but not fractions B and C, augmented insulin secretion significantly at the same level as that by BMFE. This finding was also observed in pancreatic islets. In OGTT, BMFE and fraction A decreased blood glucose levels and increased serum insulin levels after glucose loading. The decrease in blood glucose levels was also observed in streptozotocin-induced diabetic rats. In addition, BMFE and fraction A increased the ATP content in β-cells. We concluded that hydrophobic components of BMFE increase ATP production and augment insulin secretion from β-cells, consequently decreasing blood glucose levels.