Reduced expression of PDX-1 is associated with decreased beta cell function in chronic pancreatitis.

Abstract:

OBJECTIVES:The present study was conducted to monitor the expression of pancreas and duodenal homeobox gene (PDX-1) for assessing beta-cell function in islets from patients with chronic pancreatitis (CP). METHODS:Islets isolated from the pancreata of 40 surgical patients categorized as control group, patients with mild CP, and patients with advanced CP were assessed for their yield, size, and glucose-stimulated insulin secretion. Expressions of genes coding for PDX-1, insulin, and glucagon were simultaneously monitored by reverse transcription polymerase chain reaction and confirmed by immunohistochemistry. RESULTS:In comparison with the control group (2673 +/- 592 islet equivalents [IEq]/g), islet yield did not differ much in the patients with mild CP (2344 +/- 738 IEq/g) but was significantly reduced (P < 0.0001) in the patients with advanced CP (731 +/- 167 IEq/g). Although the marginal decrease in islet size observed in the patients with mild CP was not significantly different from that observed in the control group, there was a 58% decrease observed in the patients with advanced CP that was also accompanied by a significant reduction in beta-cell mass (P < 0.05). The expression of insulin and PDX-1 genes, but not of glucagon, was significantly reduced in the patients with advanced CP as confirmed by immunohistochemistry. Islets obtained from the patients with advanced CP retained 53% glucose-stimulated insulin secretion function in comparison with those of the control group. CONCLUSION:The results indicate that beta-cell dysfunction during progression of CP correlates with the decrease in PDX-1 gene expression.

journal_name

Pancreas

journal_title

Pancreas

authors

Mitnala S,Pondugala PK,Guduru VR,Rabella P,Thiyyari J,Chivukula S,Boddupalli S,Hardikar AA,Reddy DN

doi

10.1097/MPA.0b013e3181d6bc69

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

856-62

issue

6

eissn

0885-3177

issn

1536-4828

journal_volume

39

pub_type

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