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


CONCLUSIONS
The results indicate that beta-cell dysfunction during progression of CP correlates with the decrease in PDX-1 gene expression.
Mitnala
Sasikala
S
Asian Health Care Foundation, Somajiguda, Hyderabad 500082, India. aigres.mit@gmail.com
Pondugala
Pavan Kumar
PK
Guduru
Venkat Rao
VR
Rabella
Pradeep
P
Thiyyari
Jayashree
J
Chivukula
Subramanyam
S
Boddupalli
Sadasivudu
S
Hardikar
Anandwardhan A
AA
Reddy
Duvvuru Nageshwar
DN
D000328:Adult; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon; D005947:Glucose