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

Objectives: The present study was conducted to monitor the expression of pancreas and duodenal homeobox gene (PDX-1) for assessing β-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 β-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 β-cell dysfunction during progression of CP correlates with the decrease in PDX-1 gene expression.