Epidermal growth factor and gastrin on PDX1 expression in experimental type 1 diabetic rats

Am J Med Sci. 2012 Feb;343(2):141-145. doi: 10.1097/MAJ.0b013e31822423793.

Abstract

Introduction: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process.

Methods: Rat diabetes was induced by intraperitoneal injection of STZ. The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Serum levels of C-peptide and insulin were analyzed using radioimmunoassay kits.

Results: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products.

Conclusions: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology
  • Drug Combinations
  • Epidermal Growth Factor / administration & dosage*
  • Gastrins / administration & dosage*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Hyperglycemia / drug therapy
  • Hyperglycemia / physiopathology
  • Injections, Subcutaneous / veterinary
  • Insulin / blood
  • Islets of Langerhans / physiopathology
  • Male
  • RNA, Messenger / metabolism
  • Radioimmunoassay / veterinary
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction / veterinary
  • Reverse Transcriptase Polymerase Chain Reaction / veterinary
  • Trans-Activators / metabolism*

Substances

  • C-Peptide
  • Drug Combinations
  • Gastrins
  • Homeodomain Proteins
  • Insulin
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Epidermal Growth Factor