Islet neogenesis associated protein transgenic mice are resistant to hyperglycemia induced by streptozotocin.
Islet neogenesis associated protein (INGAP) is a protein factor that can stimulate new islet mass from adult pancreatic progenitor cells. In models of islet neogenesis, INGAP expression is elevated in pancreatic acinar cells. Using a transgenic model to drive a sustained expression of INGAP in pancreatic acinar cells, we have identified a protection to chemical-induced hyperglycemia. A sustained expression of INGAP during development did not perturb islet development or basal blood glucose homeostasis, although beta-cell mass and pancreatic insulin content were significantly increased in the INGAP transgenic mice. When challenged with a diabetogenic dose of streptozotocin (STZ), mice carrying the INGAP transgene did not become hyperglycemic. In contrast, wild-type mice became and remained hyperglycemic, blood glucose > 550 mg/dl. The serum insulin levels and islet morphology were preserved in the transgenic mice after STZ treatment. These data suggest that the sustained expression of INGAP in the acinar pancreas confers resistance to a diabetogenic insult. The INGAP transgenic mouse provides a new model to uncover factors that are protective to diabetes onset and biomarkers to track beta-cell pathology.
Taylor-Fishwick
David A
DA
Department of Internal Medicine, Eastern Virginia Medical School, 855 W Brambleton Avenue, Norfolk, 23510 Virginia, USA. taylord@evms.edu
Bowman
Angela
A
Hamblet
Natasha
N
Bernard
Paul
P
Harlan
David M
DM
Vinik
Aaron I
AI
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control; D015870:Gene Expression; D007113:Immunity, Innate; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007328:Insulin / Q000032:analysis / Q000097:blood; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010196:Pancreatic Elastase / Q000235:genetics / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; C490252:Reg3d protein, mouse; D010196:Pancreatic Elastase