Nesfatin-1 stimulates glucagon and insulin secretion and beta cell NUCB2 is reduced in human type 2 diabetic subjects

Abstract

Nesfatin-1 is a novel anorexigenic regulatory peptide. The peptide is the N-terminal part of nucleobindin 2 (NUCB2) and is expressed in brain areas regulating feeding. Outside the brain, nesfatin-1 expression has been reported in adipocytes, gastric endocrine cells and islet cells. We studied NUCB2 expression in human and rodent islets using immunocytochemistry, in situ hybridization and western blot. Furthermore, we investigated the potential influence of nesfatin-1 on secretion of insulin and glucagon in vitro and in vivo in mice and in INS-1 (832/13) cells. The impact of type 2 diabetes (T2D) and glucolipotoxicity on NUCB2 gene expression in human islets and its relationship to insulin secretory capacity and islet gene expression was studied using microarray. Nesfatin-1 immunoreactivity (IR) was abundant in human and rodent beta cells but absent in alpha, delta, PP and ghrelin cells. Importantly, in situ hybridization showed that NUCB2 mRNA is expressed in human and rat islets. Western blot analysis showed that nesfatin-1 IR represented full length NUCB2 in rodent islets. Human islet NUCB2 mRNA was reduced in T2D subjects but upregulated after culture in glucolipotoxic conditions. Furthermore, a positive correlation between NUCB2 and glucagon and insulin gene expression, as well as insulin secretory capacity, was evident. Nesfatin-1 enhanced glucagon secretion but had no effect on insulin secretion from mouse islets or INS-1 (832/13) cells. On the other hand, nesfatin-1 caused a small increase in insulin secretion and reduced glucose during IVGTT in mice. We conclude that nesfatin-1 is a novel glucagon-stimulatory peptide expressed in the beta cell and that its expression is decreased in T2D islets.

Increased Serum Nesfatin-1 Levels in Patients with Impaired Glucose Tolerance

“…Their data suggested that nesfatin-1 is a novel glucagon-stimulatory factor in the beta cells and that its expression is decreased in the islets of type 2 DM patients (14). The results of our study reflect a possible defensive increase in the plasma nesfatin-1 concentration to regulate the impaired glucose metabolism in IGT patients, which is later corrupted by the development of diabetes.…”

“…They explained that insulin resistance might be the possible reason for the increased levels of nesfatin-1 in newly diagnosed type 2 diabetic patients. Riva et al (14) reported that nesfatin-1 increased the glucagon secretion in vitro and insulin secretion in vivo in mice. They demonstrated that NUCB2 is expressed in human and rodent beta cells and that Akın …”

Recent progress in research on the distribution and function of NUCB2/Nesfatin-1 in peripheral tissues [Review]

“…However, the mean fasting plasma Nesfatin-1 levels were slightly but not significantly higher in T1DM patients compared to those in healthy subjects. In the study by Riva et al [21], the microarray and RT-PCR results confirmed that NUCB2 gene expression decreased in the islets of T2DM patients and that expression was enhanced under glucolipotoxic conditions in human pancreatic specimens. This finding suggested that the secretion mechanism of Nesfatin-1 in islets correlated positively with insulin secretory capacity.…”

“…Additional in vivo and in vitro studies also confirmed that Nesfatin-1 increased insulin secretion and glucose elimination in mice [21,22,23]. Riva et al [21] also identified that Nesfatin-1 was present in islet β-cells, but it augmented glucagon secretion independently the concentration of glucose in vitro, meanwhile increased insulin secretion and improved glucose elimination in vivo.…”

“…Riva et al [21] also identified that Nesfatin-1 was present in islet β-cells, but it augmented glucagon secretion independently the concentration of glucose in vitro, meanwhile increased insulin secretion and improved glucose elimination in vivo.…”