Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells.

Abstract

Nesfatin-1 is a recently discovered multifunctional metabolic hormone abundantly expressed in the pancreatic islets. The main objective of this study is to characterize the direct effects of nesfatin-1 on insulin secretion in vitro using MIN6 cells and islets isolated from C57BL/6 mice. We also examined the expression of the nesfatin-1 precursor protein, nucleobindin 2 (NUCB2) mRNA, and nesfatin-1 immunoreactivity (ir) in the islets of normal mice and in the islets from mice with streptozotocin-induced type 1 diabetes and diet-induced obese (DIO) mice with type 2 diabetes. Nesfatin-1 stimulated glucose-induced insulin release in vitro from mouse islets and MIN6 cells in a dose-dependent manner. No such stimulation in insulin secretion was found when MIN6 cells/islets were incubated with nesfatin-1 in low glucose. In addition, a fourfold increase in nesfatin-1 release from MIN6 cells was observed following incubation in high glucose (16.7  mM) compared to low glucose (2  mM). Furthermore, we observed a significant reduction in both NUCB2 mRNA expression and nesfatin-1-ir in the pancreatic islets of mice with type 1 diabetes, while a significant increase was observed in the islets of DIO mice. Together, our findings indicate that nesfatin-1 is a novel insulinotropic peptide and that the endogenous pancreatic islet NUCB2/nesfatin is altered in diabetes and diet-induced obesity.

• Authors: Ronald Gonzalez, Benjamin K Reingold, Xiaodong Gao, Mandeep P Gaidhu, Robert G Tsushima, Suraj Unniappan
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 208 Issue 3 Pg. R9-R16 (Mar 2011) ISSN: 1479-6805 [Electronic] England
• PMID: 21224288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• DNA-Binding Proteins
• Insulin
• Nerve Tissue Proteins
• Nucb1 protein, mouse
• Nucleobindins
• Glucagon
• Glucose

Topics

• Animals
• Calcium-Binding Proteins (metabolism)
• Cell Line
• Cells, Cultured
• DNA-Binding Proteins (metabolism)
• Diabetes Mellitus, Experimental (metabolism)
• Diabetes Mellitus, Type 1 (metabolism)
• Diabetes Mellitus, Type 2 (metabolism)
• Glucagon (metabolism)
• Glucose (metabolism)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nerve Tissue Proteins (metabolism, pharmacology)
• Nucleobindins
• Obesity (metabolism)