Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs

Pancreas. 2007 Jan;34(1):103-11. doi: 10.1097/01.mpa.0000240609.56806.43.


Objectives: Diabetes is a serious health problem. It has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs.

Methods: Forty nondiabetic beagle dogs were randomly divided into 4 groups. Group 1 received daily intramuscular injections of vehicle, whereas the other 3 groups received daily INGAP injections of 0.5, 1.5, or 10 mg/kg. After 30 days, pancreatic tissues were collected, and RNA and histological sections were analyzed.

Results: In dogs treated with 1.5 mg/kg INGAP, there was a significant (P < 0.001) increase in the percentage of insulin-positive cells (P < 0.001) and insulin gene expression. There was a trend to increased insulin-positive cells and gene expression with treatments of 0.5 and 10 mg/kg peptide. Protein gene product 9.5-positive cells were increased with treatment.

Conclusions: These results indicate that INGAP stimulates cells in the pancreatic duct epithelium of healthy dogs (putative islet progenitor cells) to develop along a neuroendocrine pathway and form new islets in response to INGAP peptide. The INGAP might be an effective therapy for diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / pharmacology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / pharmacokinetics
  • Biomarkers, Tumor / pharmacology*
  • Cell Division / drug effects
  • Cricetinae
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dogs
  • Female
  • Fluorescent Antibody Technique
  • Injections, Intramuscular
  • Injections, Intravenous
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Lectins, C-Type / genetics
  • Male
  • Mesocricetus
  • Pancreatitis-Associated Proteins
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / pharmacology
  • Regeneration / drug effects


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • REG3A protein, human
  • RNA, Messenger
  • Recombinant Fusion Proteins