β-Cell Dedifferentiation in Patients With T2D With Adequate Glucose Control and Nondiabetic Chronic Pancreatitis
J Sun, Q Ni, J Xie, M Xu, J Zhang… - The Journal of …, 2019 - academic.oup.com
J Sun, Q Ni, J Xie, M Xu, J Zhang, J Kuang, Y Wang, G Ning, Q Wang
The Journal of Clinical Endocrinology & Metabolism, 2019•academic.oup.comAbstract 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 …
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 …
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.
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