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

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.

• Authors: Jiajun Sun, Qicheng Ni, Jing Xie, Min Xu, Jun Zhang, Jie Kuang, Yanqiu Wang, Guang Ning, Qidi Wang
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 1 Pg. 83-94 (01 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 30085195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose

Topics

• Aged
• Atrophy
• Blood Glucose
• Cell Dedifferentiation
• Diabetes Mellitus, Type 2 (blood, complications, pathology)
• Female
• Fibrosis
• Humans
• Inflammation (pathology)
• Insulin-Secreting Cells (pathology)
• Islets of Langerhans (pathology)
• Male
• Middle Aged
• Pancreatitis, Chronic (blood, complications, pathology)