The cytotoxic role of intermittent high glucose on apoptosis and cell viability in pancreatic beta cells.

Zhen Zhang,Lei Yang,Hong Chen,Rongping Chen,Dehong Cai,Jing Li,Rui Yang,Hua Zhang

doi:10.1155/2014/712781

Zhen Zhang, Lei Yang + Show 6 more

Open Access

https://doi.org/10.1155/2014/712781

Copy DOI

Abstract

Objectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. Methods. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined. Results. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly. Conclusions. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.

Highlights

Diabetes is becoming a serious worldwide threat to human health and rises rapidly in China recently
Pancreatic β-cell mass should be dynamic and can respond to physiological and pathological variations in metabolic demand on insulin production. This ability of the endocrine pancreas seems to be attenuated in type 2 diabetes which leads to hyperglycemia and blood glucose fluctuations [1,2,3]
Both animal and human studies have demonstrated that increase of β-cell apoptosis is an important reason for insulin deficiency in T2DM, which leads to hyperglycemia and blood glucose fluctuations [4, 5, 18]

Summary

Introduction

Diabetes is becoming a serious worldwide threat to human health and rises rapidly in China recently. Pancreatic β-cell mass should be dynamic and can respond to physiological and pathological variations in metabolic demand on insulin production. This ability of the endocrine pancreas seems to be attenuated in type 2 diabetes which leads to hyperglycemia and blood glucose fluctuations [1,2,3]. Evidence from autopsy demonstrated that β-cell mass in diabetic patients is significantly reduced and its reduction is associated with increased apoptosis [4, 5]. Glucose control may become deteriorated despite intensive treatment in diabetic patients because their pancreatic beta cell mass decreased abnormally. The patients with long duration of diabetes will be prone to show a higher glucose variation [6, 7]

Objectives

Methods

Results

Conclusion