Involvement of Oxidative Stress–Induced DNA Damage, Endoplasmic Reticulum Stress, and Autophagy Deficits in the Decline of β-Cell Mass in Japanese Type 2 Diabetic Patients

• DOI: 10.2337/dc13-2018
• Publication Date: 2014-04-05T03:06:18Z
• Authors: Hiroki Mizukami; Kazunori Takahashi; Wataru Inaba; Kentaro Tsuboi; Sho Osonoi; Taro Yoshida; Soroku Yagihashi
• Keywords: Male; 0301 basic medicine; Middle Aged; Endoplasmic Reticulum Stress; 3. Good health; Oxidative Stress; 03 medical and health sciences; Asian People; Diabetes Mellitus, Type 2; Japan; Insulin-Secreting Cells; Autophagy; Humans; Female; Autopsy; Pancreas; Aged; DNA Damage

Deficits of β-cells characterize the islet pathology in type 2 diabetes. It is yet to be clear how β-cell loss develops We explored implication oxidative stress, endoplasmic reticulum (ER)-induced and autophagy deficit decline Japanese diabetic patients.Pancreases from recent autopsy cases 47 30 nondiabetic subjects were investigated on structure with morphometric analysis. Volume densities (Vi), (Vβ), α-cell (Vα) measured. To evaluate cell damage endocrine cells, immunohistochemical expressions stress-related DNA as expressed by γH2AX, ER CCAAT/enhancer 1 binding protein-β (C/EBP-β), P62 semiquantified, their correlations changes sought.Compared subjects, Vβ was reduced subjects. Contrariwise, there an increase Vα. There a significant link between increased HbA1c levels (P < 0.01) trend inverse correlation duration diabetes = 0.06). Expressions P62, C/EBP-β all enhanced islets, correlated intensity γH2AX expression but not or expressions. Combined associated severe reduction Vβ.β-Cell stress may further augmented autophagic deficits stress.