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



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



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.



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.



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.



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.
McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030.
Carol J
CJ
Lam
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Daniel R
DR
Jacobson
Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Matthew M
MM
Rankin
McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030.
Aaron R
AR
Cox
McNair Medical Institute, Pediatric Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030.|Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Jake A
JA
Kushner
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D054338:Cell Transdifferentiation; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D012038:Regeneration; D013997:Time Factors; D055815:Young Adult
D007328:Insulin; D019394:Ki-67 Antigen; D005934:Glucagon