SUN-N8075

VGF nerve growth factor inducible (VGF) is a secreted polypeptide involved in metabolic regulation. VGF-derived peptides have been reported to regulate insulin secretion in the plasma of patients with type 2 diabetes and model mice. However, the protective effects of VGF on pancreatic β-cells in diabetic model are not well understood. In this study, we aimed to elucidate the β-cell protective effect of VGF on a streptozotocin (STZ)-induced diabetic model using VGF-overexpressing (OE) mice and also examined the therapeutic effect by a small molecule, SUN N8075 which is an inducer of VGF. VGF-OE mice improved blood glucose levels and maintained β-cell mass compared to wild-type (WT) mice on STZ-induced diabetic model. In addition, VGF-OE mice showed better glucose tolerance than WT mice. In culture, AQEE-30, a VGF-derived peptide, suppressed STZ-induced β-cell death in vitro and attenuated the decrease in the phosphorylation of Akt and GSK3β. Furthermore, SUN N8075 suppressed the blood glucose levels and increased VGF expression in the pancreatic islet. SUN N8075 also protected STZ-induced β-cell death in vitro. These findings indicate that VGF plays a hypoglycemic role in response to blood glucose levels in diabetes and protects β-cells from STZ-induced cell death. Therefore, VGF and its inducer have the therapeutic potential by preserving β-cells in diabetes.