SNAPIN Regulates Cell Cycle Progression to Promote Pancreatic β Cell Growth.

Mengxue Jiang,Yaohui He,Jidong Cheng,Tingyan Yu,Zhijian Kuang,Wen Liu,Wei Wang,Yin Cao

doi:10.3389/fendo.2021.624309

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.

Highlights

Diabetes is a prevalent disease worldwide, and it has become a serious social health problem [1]
The function of SNAPIN in b cell growth is poorly understood, and our findings reveal that the overexpression of SNAPIN in Min6 cells can promote cell proliferation and is promising in achieving the goals of regenerative medicine for diabetes treatment
We investigated SNAPIN expression by immunostaining, and diabetes mice had much less SNAPIN compared with WT controls (Figures 1F, G)

Summary

Introduction

Diabetes is a prevalent disease worldwide, and it has become a serious social health problem [1]. It results in a deficiency of functional pancreatic b cells [2].The maintenance of b-cell number and islet mass is essential for maintaining normoglycemia [3, 4]. Type 1 diabetes mellitus (T1DM) is associated with impaired b cell mass [6].The pathogenesis of type 2 diabetes is more variable, and it consists of insulin resistance and defective insulin secretion [6]. During pregnancy and the early stages of diabetes, compensatory proliferation of pancreatic b cells occurs in response to changes in blood glucose [8, 9]. Glucose itself is able to stimulate b cell replication [10], and several lines of evidence indicate that the terminally differentiated pancreatic b cells retain significantly proliferative capacity

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