Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2019 Jan 1;104(1):83-94. doi: 10.1210/jc.2018-00968.

β-Cell Dedifferentiation in Patients With T2D With Adequate Glucose Control and Nondiabetic Chronic Pancreatitis.

Sun J1,2, Ni Q1,2, Xie J3, Xu M1,2, Zhang J4, Kuang J4, Wang Y1,2, Ning G1,2, Wang Q1,2,5.

Author information

1
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Shanghai Key Laboratory for Endocrine Tumors and E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3
Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5
Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Context:

Type 2 diabetes (T2D) and pancreatogenic diabetes are both associated with loss of functional β-cell mass. Previous studies have proposed β-cell dedifferentiation as a mechanism of islet β-cell failure, but its significance in humans is still controversial.

Objective:

To determine whether β-cell dedifferentiation occurs in human T2D with adequate glucose control and in nondiabetic chronic pancreatitis (NDCP), we examined pancreatic islets from nine nondiabetic controls, 10 patients with diabetes with well-controlled fasting glycemia, and four individuals with NDCP.

Design:

We calculated the percentage of hormone-negative endocrine cells and multihormone endocrine cells and scored the pathological characteristics; that is, inflammatory cell infiltration, fibrosis, atrophy, and steatosis, in each case.

Results:

We found a nearly threefold increase in dedifferentiated cells in T2D with adequate glucose control compared with nondiabetic controls (10.0% vs 3.6%, T2D vs nondiabetic controls, P < 0.0001). The dedifferentiation rate was positively correlated with the duration of diabetes. Moreover, we detected a considerable proportion of dedifferentiated cells in NDCP (10.4%), which correlated well with the grade of inflammatory cell infiltration, fibrosis, and atrophy.

Conclusions:

The data support the view that pancreatic β-cells are dedifferentiated in patients with T2D with adequate glucose control. Furthermore, the existence of abundant dedifferentiated cells in NDCP suggests that inflammation-induced β-cell dedifferentiation can be a cause of pancreatogenic diabetes during disease progress.

PMID:
30085195
DOI:
10.1210/jc.2018-00968

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center