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J Clin Endocrinol Metab. 2017 Aug 1;102(8):2647-2659. doi: 10.1210/jc.2016-3806.

β Cells Persist in T1D Pancreata Without Evidence of Ongoing β-Cell Turnover or Neogenesis.

Author information

1
McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030.
2
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.

Abstract

Context:

The cellular basis of persistent β-cell function in type 1 diabetes (T1D) remains enigmatic. No extensive quantitative β-cell studies of T1D pancreata have been performed to test for ongoing β-cell regeneration or neogenesis.

Objective:

We sought to determine the mechanism of β-cell persistence in T1D pancreata.

Design:

We studied T1D (n = 47) and nondiabetic control (n = 59) pancreata over a wide range of ages from the Juvenile Diabetes Research Foundation Network of Pancreatic Organ Donors with Diabetes via high-throughput microscopy.

Intervention and Main Outcome Measures:

We quantified β-cell mass, β-cell turnover [via Ki-67 and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL)], islet ductal association, and insulin/glucagon coexpression in T1D and control pancreata.

Results:

Residual insulin-producing β cells were detected in some (but not all) T1D cases of varying disease duration. Several T1D pancreata had substantial numbers of β cells. Although β-cell proliferation was prominent early in life, it dramatically declined after infancy in both nondiabetic controls and T1D individuals. However, β-cell proliferation was equivalent in control and T1D pancreata. β-cell death (assessed by TUNEL) was extremely rare in control and T1D pancreata. Thus, β-cell turnover was not increased in T1D. Furthermore, we found no evidence of small islet/ductal neogenesis or α-cell to β-cell transdifferentiation in T1D pancreata, regardless of disease duration.

Conclusion:

Longstanding β-cell function in patients with T1D appears to be largely a result of β cells that persist, without any evidence of attempted β-cell regeneration, small islet/ductal neogenesis, or transdifferentiation from other islet endocrine cell types.

PMID:
28323930
PMCID:
PMC5546851
DOI:
10.1210/jc.2016-3806
[Indexed for MEDLINE]
Free PMC Article

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