Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes.
Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing β-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown.



To investigate the PDG compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of β-cells.



Pancreases from 46 brain dead organ donors (22 with T1D, 24 nondiabetic controls) were investigated for activation (increased proliferation) and markers of pancreatic exocrine and endocrine progenitors.



PDG cell replication was increased in T1D (6.3% ± 1.6% vs 0.6% ± 0.1%, P < 0.001, T1D vs nondiabetic), most prominently in association with pancreatic inflammation. There were increased progenitor-like cells in PDGs of T1D, but predominantly with an exocrine fate.



The PDG compartment is activated in T1D consistent with a response to ongoing inflammation, and via resulting ductal hyperplasia may contribute to local obstructive pancreatitis and eventual pancreatic atrophy characteristic of T1D. However, there is no evidence of effective endocrine cell formation from PDGs.
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095.
Abu Saleh Md
AS
Moin
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095.
Peter C
PC
Butler
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095.
Alexandra E
AE
Butler
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D046790:Pancreas, Exocrine / Q000378:metabolism / Q000473:pathology*; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D015415:Biomarkers