SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth

Abstract

In diabetes mellitus, death of β cell in the pancreas occurs throughout the development of the disease, with loss of insulin production. The maintenance of β cell number is essential to maintaining normoglycemia. SNAPIN has been found to regulate insulin secretion, but whether it induces β cell proliferation remains to be elucidated. This study aimed to explore the physiological roles of SNAPIN in β cell proliferation. SNAPIN expression increases with the age of mice and SNAPIN is down-regulated in diabetes. KEGG pathway and GO analysis showed that SNAPIN- interacting proteins were enriched in cell cycle regulation. B cell cycle was arrested in the S phase, and cell proliferation was inhibited after SNAPIN knockdown. The expression of CDK2, CDK4 and CCND1 proteins in the S phase of the cell cycle were reduced after SNAPIN knockdown, whereas they were increased after overexpression of SNAPIN. In addition, insulin protein and mRNA levels also increased or decreased after SNAPIN knockdown or overexpression, respectively. Conclusions: Our data indicate that SNAPIN mediates β cells proliferation and insulin secretion, and provide evidences that SNAPIN might be a pharmacotherapeutic target for diabetes mellitus.

Study on the active ingredients and mechanism of action of Jiaotai Pill in the treatment of type 2 diabetes based on network pharmacology: A review

“…[ 39 , 40 ] Studies have found that CCND1 plays a role in obesity-related T2DM, which is related to its participation in fatty acid and glucose metabolic pathways and oxidation/reduction reactions [ 41 ] ; while CDK4/6 has a regulatory effect on human beta cell proliferation. [ 42 ] Studies have found that CDK1 is the key to drive oxidative phosphorylation, and the abnormal increase in the secretion of oxidative phosphorylation components may be the basis for the development of diabetes. [ 43 ] In the pathogenesis of T2DM, the increase or decrease of the above targets plays an important role in the occurrence, development and treatment of T2DM.…”

Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathway via IRS2-proteasome degradation

“…After transfection for two days, the UA+IRS2 group was treated with 15 mg/dL of UA for 24 h, and then the cells were subjected to IP as mentioned above. LC-MS analysis was executed according to our previously described method ( 32 ). The peptides were desalted by StageTips ( 33 , 34 ).…”