Decreased Hepatic Phosphatidylinositol-3,4,5-Triphosphate (PIP3) Levels and Impaired Glucose Homeostasis in Type 1 and Type 2 Diabetic Rats

Abstract

Background/Aims: Phosphatidylinositol-3,4,5-triphosphate (PIP3) and phosphatidylinositol-4,5-biphosphate (PIP2) are two well-known lipid second messengers. Polyphosphoinositides have been implicated in the regulation of the signal transduction pathways involved in glucose metabolism using cell culture studies. However, there are no in vivo studies in the literature investigating the status of PIP3 and PIP2 in any of the tissues of diabetic animals. The liver plays an important role in the regulation of whole body glucose homeostasis. This study investigated whether hepatic PIP3 and/or PIP2 levels are altered in diabetes. Methods: Experiments were performed in streptozotocin-treated type 1 (T1D) and ZDF type 2 (T2D) diabetic rats. Blood glucose was determined utilizing glucose oxidase, glycosylated hemoglobin (GHb) using Glyco-Tek Affinity columns, and hepatic PIP3 and PIP2 concentrations by sandwich ELISA, and Akt phosphorylation and GLUT2 protein abundance by Western blotting. Results: Blood glucose and GHb were higher in T1D and T2D rats compared to controls. As compared to control animals, in livers from T1D and T2D rats PIP3 levels were reduced, AKT phosphorylation downregulated, and GLUT2 protein expression increased. PIP2 levels were unchanged. Conclusion: PIP3 is decreased, AKT phosphorylation downregulated, GLUT2 protein expression increased and glucose homeostasis altered in livers of type 1 and type 2 diabetic rats.