Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

A. E. Butler; R. Galasso; A. Matveyenko; R. A. Rizza; S. Dry; P. C. Butler

doi:10.1007/s00125-009-1556-8

Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

A. E. Butler, R. Galasso, A. Matveyenko, R. A. Rizza, S. Dry, P. C. Butler

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

Aims/hypothesis: 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/m²); 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/interpretation: 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.

Original language	English (US)
Pages (from-to)	21-26
Number of pages	6
Journal	Diabetologia
Volume	53
Issue number	1
DOIs	https://doi.org/10.1007/s00125-009-1556-8
State	Published - Jan 2010

Keywords

DPP-IV inhibitor
GLP-1
Obesity
Pancreatic cancer
Pancreatic ductal
Pancreatitis

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.1007/s00125-009-1556-8

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title = "Pancreatic duct replication is increased with obesity and type 2 diabetes in humans",

abstract = "Aims/hypothesis: 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/m2); 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/interpretation: 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.",

keywords = "DPP-IV inhibitor, GLP-1, Obesity, Pancreatic cancer, Pancreatic ductal, Pancreatitis",

author = "Butler, {A. E.} and R. Galasso and A. Matveyenko and Rizza, {R. A.} and S. Dry and Butler, {P. C.}",

note = "Funding Information: Acknowledgements This study was supported by funding from the NIH (DK059579, DK077967) and the Larry L. Hillblom Foundation. We are grateful to our colleagues A. Bhushan and S. Georgia in the Larry Hillblom Islet Research Center for their excellent suggestions. We acknowledge B. Lui for excellent administrative assistance.",

year = "2010",

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doi = "10.1007/s00125-009-1556-8",

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T1 - Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

AU - Butler, A. E.

AU - Galasso, R.

AU - Matveyenko, A.

AU - Rizza, R. A.

AU - Dry, S.

AU - Butler, P. C.

N1 - Funding Information: Acknowledgements This study was supported by funding from the NIH (DK059579, DK077967) and the Larry L. Hillblom Foundation. We are grateful to our colleagues A. Bhushan and S. Georgia in the Larry Hillblom Islet Research Center for their excellent suggestions. We acknowledge B. Lui for excellent administrative assistance.

PY - 2010/1

Y1 - 2010/1

N2 - Aims/hypothesis: 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/m2); 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/interpretation: 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.

AB - Aims/hypothesis: 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/m2); 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/interpretation: 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.

KW - DPP-IV inhibitor

KW - GLP-1

KW - Obesity

KW - Pancreatic cancer

KW - Pancreatic ductal

KW - Pancreatitis

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Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

Abstract

Keywords

ASJC Scopus subject areas

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