Targeted expression of islet neogenesis associated protein to beta cells enhances glucose tolerance and confers resistance to streptozotocin-induced hyperglycemia

Mol Cell Endocrinol. 2011 Mar 30;335(2):104-9. doi: 10.1016/j.mce.2010.12.026. Epub 2010 Dec 25.


Islet neogenesis associated protein (INGAP) stimulates experimental pancreatic islet growth, as evidenced by elevated markers of beta cell mass, in rodents, dogs and primates. Previous analyses of mice that have a transgenic expression of INGAP targeted to the exocrine pancreas have indicated additional biological activity attributed to INGAP. In this study we report on mice with a targeted expression of INGAP to the islet beta cell. The beta cell transgenic mice (IP-INGAP) showed enhanced normalization of blood glucose during IPGTT. Further, IP-INGAP mice had a significant delay in development of hyperglycemia following a diabetogenic dose of streptozotocin. INGAP conferred beta cell protection and enhanced islet function. Analysis of oxidative stress genes in IP-INGAP mice revealed a decrease in islet expression of the NADPH oxidase, NOX1, in both basal state and in response to pro-inflammatory cytokine stimulation. These data are consistent with a pleiotropic role for INGAP and reveal new pathways to target in the discovery of improved diabetic therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental / chemically induced*
  • Diabetes Mellitus, Experimental / metabolism
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Hyperglycemia / chemically induced*
  • Hyperglycemia / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • NADH, NADPH Oxidoreductases / genetics
  • NADPH Oxidase 1
  • Pancreatitis-Associated Proteins
  • Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Streptozocin
  • Transcription, Genetic


  • Blood Glucose
  • Insulin
  • Pancreatitis-Associated Proteins
  • Proteins
  • REG3A protein, human
  • Recombinant Proteins
  • Reg3b protein, mouse
  • Streptozocin
  • NADH, NADPH Oxidoreductases
  • NADPH Oxidase 1
  • NOX1 protein, mouse
  • Caspase 3
  • Glucose