Is β-cell aging involved in the pathogenesis of diabetes?
BACKGROUND
β-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in β-cell phonotype in the development of diabetes to identify potential β-cell targets to prevent the progression of diabetes.


METHODS
A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non-diabetics (ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of β-cell mass. Insulin-positive duct cells and scattered β-cells were defined as newly generated β-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) and insulin/P16 double-positive cells were defined as immature, mature, and senescent β-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test.


RESULTS
There were no significant differences in β-cell mass, the prevalence of insulin-positive duct cells, scattered β-cells, or insulin/Ngn3, insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/P16 double-positive cells was significantly higher in T2D than ND. β-Cell apoptosis was significantly higher in T2D and IFG than ND.


CONCLUSIONS
The senescence and apoptosis of β-cells may be involved in the course of diabetes.
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Junping
J
Wen
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Ting
T
Xue
Department of Pathology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
Ying
Y
Huang
Department of Pathology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
Xiaoyan
X
Chen
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Ying
Y
Xue
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Wei
W
Lin
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Lizhen
L
Zhang
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Jin
J
Yao
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Huibin
H
Huang
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Jixing
J
Liang
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Liantao
L
Li
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Lixiang
L
Lin
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Lidan
L
Shi
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Liangchun
L
Cai
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Zhuangli
Z
Zhu
Department of Endocrinology, Fujian Provincial Hospital, Fujian Academy of Medical Sciences and, Fujian Medical University, Fuzhou, China.
Gang
G
Chen
D000328:Adult; D000368:Aged; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D016922:Cellular Senescence; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012189:Retrospective Studies
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D019394:Ki-67 Antigen; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; C485159:MAFA protein, human; C498695:NEUROG3 protein, human
2型糖尿病; apoptosis; pancreatic β-cells; senescence; type 2 diabetes mellitus; 凋亡; 胰腺β细胞; 衰老