title: Reduced expression of PDX-1 is associated with decreased beta cell function in chronic pancreatitis.
abstract: 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.
authors.affiliation: Asian Health Care Foundation, Somajiguda, Hyderabad 500082, India. aigres.mit@gmail.com
authors.forename: Sasikala
authors.initials: S
authors.lastname: Mitnala
authors.forename: Pavan Kumar
authors.initials: PK
authors.lastname: Pondugala
authors.forename: Venkat Rao
authors.initials: VR
authors.lastname: Guduru
authors.forename: Pradeep
authors.initials: P
authors.lastname: Rabella
authors.forename: Jayashree
authors.initials: J
authors.lastname: Thiyyari
authors.forename: Subramanyam
authors.initials: S
authors.lastname: Chivukula
authors.forename: Sadasivudu
authors.initials: S
authors.lastname: Boddupalli
authors.forename: Anandwardhan A
authors.initials: AA
authors.lastname: Hardikar
authors.forename: Duvvuru Nageshwar
authors.initials: DN
authors.lastname: Reddy
mesh_terms: 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
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon; D005947:Glucose