PMID- 28323930
OWN - NLM
STAT- MEDLINE
DCOM- 20170920
LR  - 20181113
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 102
IP  - 8
DP  - 2017 Aug 1
TI  - beta Cells Persist in T1D Pancreata Without Evidence of Ongoing beta-Cell Turnover or 
      Neogenesis.
PG  - 2647-2659
LID - 10.1210/jc.2016-3806 [doi]
AB  - CONTEXT: The cellular basis of persistent beta-cell function in type 1 diabetes 
      (T1D) remains enigmatic. No extensive quantitative beta-cell studies of T1D 
      pancreata have been performed to test for ongoing beta-cell regeneration or 
      neogenesis. OBJECTIVE: We sought to determine the mechanism of beta-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 beta-cell mass, 
      beta-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 beta 
      cells were detected in some (but not all) T1D cases of varying disease duration. 
      Several T1D pancreata had substantial numbers of beta cells. Although beta-cell 
      proliferation was prominent early in life, it dramatically declined after infancy 
      in both nondiabetic controls and T1D individuals. However, beta-cell proliferation 
      was equivalent in control and T1D pancreata. beta-cell death (assessed by TUNEL) was 
      extremely rare in control and T1D pancreata. Thus, beta-cell turnover was not 
      increased in T1D. Furthermore, we found no evidence of small islet/ductal 
      neogenesis or alpha-cell to beta-cell transdifferentiation in T1D pancreata, regardless 
      of disease duration. CONCLUSION: Longstanding beta-cell function in patients with 
      T1D appears to be largely a result of beta cells that persist, without any evidence 
      of attempted beta-cell regeneration, small islet/ductal neogenesis, or 
      transdifferentiation from other islet endocrine cell types.
CI  - Copyright (c) 2017 by the Endocrine Society
FAU - Lam, Carol J
AU  - Lam CJ
AD  - McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of 
      Medicine, Texas Children's Hospital, Houston, Texas 77030.
FAU - Jacobson, Daniel R
AU  - Jacobson DR
AD  - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 
      University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
FAU - Rankin, Matthew M
AU  - Rankin MM
AD  - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 
      University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
FAU - Cox, Aaron R
AU  - Cox AR
AD  - McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of 
      Medicine, Texas Children's Hospital, Houston, Texas 77030.
FAU - Kushner, Jake A
AU  - Kushner JA
AD  - McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of 
      Medicine, Texas Children's Hospital, Houston, Texas 77030.
AD  - Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 
      University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
LA  - eng
GR  - P30 DK079638/DK/NIDDK NIH HHS/United States
GR  - R01 AG040110/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Insulin)
RN  - 0 (Ki-67 Antigen)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Case-Control Studies
MH  - Cell Transdifferentiation
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/metabolism/*pathology
MH  - Female
MH  - Glucagon/metabolism
MH  - Glucagon-Secreting Cells
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Infant
MH  - Infant, Newborn
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/*cytology/metabolism
MH  - Islets of Langerhans/*cytology/metabolism
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Middle Aged
MH  - Pancreas/cytology/metabolism
MH  - Regeneration
MH  - Time Factors
MH  - Young Adult
PMC - PMC5546851
EDAT- 2017/03/23 06:00
MHDA- 2017/09/21 06:00
PMCR- 2018/08/01
CRDT- 2017/03/22 06:00
PHST- 2016/11/28 00:00 [received]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/03/23 06:00 [pubmed]
PHST- 2017/09/21 06:00 [medline]
PHST- 2017/03/22 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - 3056158 [pii]
AID - jcem_20163806 [pii]
AID - 10.1210/jc.2016-3806 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2017 Aug 1;102(8):2647-2659. doi: 10.1210/jc.2016-3806.