Nicorandil improves diabetes and rat islet beta-cell damage induced by streptozotocin in vivo and in vitro

Abstract

Objective: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K þ channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet b-cell damage both in vivo and in vitro. Design and methods: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48), 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). Results: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet b-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet b-cells or RINm5F cells, and did not show an inhibitory effect on poly( ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. Conclusions: These results suggested that nicorandil improves diabetes and rat islet b-cell damage induced by STZ in vivo and in vitro. It protects islet b-cells, at least partly, via a radical scavenging effect.European Journal of Endocrinology 151 277-285

The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

“…Several reports have shown the relationship between dysfunction in K ATP channel gating and diabetes [17]. A previous study reported that nicorandil, a mitochondrial K ATP channel opener, protects from diabetes through inhibition of the production of ROS in the streptozotocin-treated rats [52]. More recently, we also observed that the HG reduces a decrease in the cardiac expression of K ATP channels and that opening of K ATP channels protects cardiac cells against the HG-induced injury, including ROS production [7].…”

Protective effect of cirsimaritin against streptozotocin-induced apoptosis in pancreatic beta cells

“…Apoptosis occurring at the onset of diabetes is considered a major causative factor. The overexpression of anti‐apoptotic proteins has been demonstrated to protect pancreatic β cells exposed to STZ . STZ also induces pancreatic β‐cell apoptosis by the activation of PARP, caspase‐3 and caspase‐9 .…”

“…The overexpression of anti‐apoptotic proteins has been demonstrated to protect pancreatic β cells exposed to STZ . STZ also induces pancreatic β‐cell apoptosis by the activation of PARP, caspase‐3 and caspase‐9 . The molecular mechanisms underlying apoptosis were divided into two types, one including the initiators (caspase‐2, caspase‐8, caspase‐9, caspase‐10) and effectors or executioners of apoptosis (caspase‐3, caspase‐6, caspase‐7) and the other including members of the anti‐apoptotic BCL‐2 protein family .…”

“…There are growing incentives to find naturally occurring nutraceuticals that inhibit the loss of pancreatic β cells or increase their function. As streptozotocin (STZ) selectively destroys pancreatic β cells, it is widely used for making a model of type 1 diabetes mellitus . The roots of Averrhoa carambola L. have been introduced to protect against STZ‐induced pancreatic β‐cell apoptosis in diabetic mice by inhibiting caspase‐3, caspase‐8, caspase‐9 and BAX and increasing the expression of the apoptosis suppressor BCL‐2 .…”

Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats

“…In human umbilical vein endothelial cells, nicorandil inhibited apoptosis induced by serum starvation by inhibiting ROS production [19]. Furthermore, nicorandil protected from diabetic through inhibition of the production of ROS stimulated by high glucose [20]. Therefore, we hypothesised that nicorandil can prevent diabetic endothelial dysfunction.…”