Gfi1 AS A NEW TARGET FOR THE TREATMENT OF HYPERGLYCEMIA AND DIABETES
Gfi1 is expressed in the pancreas, starting from the first stages of pancreatic embryonic development. Conditional knock out Gfi1 (exclusively in the pancreas) mice were found to be viable, fertile and to display a life expectancy comparable to that of control animals. Mutant mice were challenged with high fat diet and all animals displayed a rapid increase in body mass but while control mice rapidly developed a massive hyperglycemia, mutant mice remained normoglycemic. At the end of the treatment, an intraperitoneal glucose tolerance test showed that mutant mice were able to normally clear the blood of glucose in respect to the age-matched controls that showed an impaired capability. Lastly, an intraperitoneal insulin tolerance test demonstrated that mutant animals did not develop any insulin resistance upon high fat diet as seen for their control counterparts. Mutant and control mice were treated with high dose streptozotocin to ablate their ?-cells to determine the potential impact in Type I diabetes. Control animals rapidly developed acute hyperglycemia, mutant mice remained either normoglycemic or developed a temporary mild hyperglycemia from which they quickly recovered from. An inhibitor of Gfi1 could be used for the treatment of hyperglycemia, diabetes (Type 1, Type 2).