Pancreatic duct replication is increased with obesity and type 2 diabetes in humans.
OBJECTIVE
In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans.


METHODS
We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI <25 kg/m(2)); obese (BMI >27 kg/m(2)); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication.


RESULTS
We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls.


CONCLUSIONS
Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.
Butler
A E
AE
Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, CA 90024-2852, USA.
Galasso
R
R
Matveyenko
A
A
Rizza
R A
RA
Dry
S
S
Butler
P C
PC
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001344:Autopsy; D015992:Body Mass Index; D002455:Cell Division; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000473:pathology* / Q000503:physiopathology; D010183:Pancreatic Ducts / Q000473:pathology* / Q000503:physiopathology; D051381:Rats