Increased Hormone-Negative Endocrine Cells in the Pancreas in Type 1 Diabetes.
Type 1 diabetes (T1D) is characterized by a β-cell deficit due to autoimmune inflammatory-mediated β-cell destruction. It has been proposed the deficit in β-cell mass in T1D may be in part due to β-cell degranulation to chromogranin-positive, hormone-negative (CPHN) cells.



We investigated the frequency and distribution of CPHN cells in the pancreas of 15 individuals with T1D, 17 autoantibody-positive nondiabetic individuals, and 17 nondiabetic controls.



CPHN cells were present at a low frequency in the pancreas from nondiabetic and autoantibody-positive, brain-dead organ donors but are more frequently found in the pancreas from donors with T1D (islets: 1.11% ± 0.20% vs 0.26% ± 0.06 vs 0.27% ± 0.10% of islet endocrine cells, T1D vs autoantibody positive [AA+] vs nondiabetic [ND]; T1D vs AA+, and ND, P < .001). CPHN cells are most commonly found in the single cells and small clusters of endocrine cells rather than within established islets (clusters: 18.99% ± 2.09% vs 9.67% ± 1.49% vs 7.42% ± 1.26% of clustered endocrine cells, T1D vs AA+ vs ND; T1D vs AA+ and ND, P < .0001), mimicking the distribution present in neonatal pancreas.



From these observations, we conclude that CPHN cells are more frequent in T1D and, as in type 2 diabetes, are distributed in a pattern comparable with the neonatal pancreas, implying a possible attempted regeneration. In contrast to rodents, CPHN cells are insufficient to account for loss of β-cell mass in T1D.
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Abu Saleh
AS
Md Moin
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Sangeeta
S
Dhawan
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Christine
C
Shieh
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Peter C
PC
Butler
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Megan
M
Cory
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-7073.
Alexandra E
AE
Butler
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D015550:Cell Degranulation; D002864:Chromogranins / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D055098:Endocrine Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010187:Pancreatic Hormones / Q000378:metabolism*; D011379:Prognosis; D012038:Regeneration
D001323:Autoantibodies; D015415:Biomarkers; D002864:Chromogranins; D010187:Pancreatic Hormones