Renal activity of Akt kinase in experimental Type 1 diabetes

Akt kinase regulates numerous cell functions including glucosemetabolism, cell growth, survival, protein synthesis, and controlof local hemodynamics. mTOR is one of down-stream effectors ofAkt involved in the initiation of protein translation. However,renal Akt signaling in Type 1 diabetes (DM) in vivo, in particularunder the conditions reflecting differences in metabolic control,has received less attention. Renal cortical activity and expressionof Akt and mTOR (kinase assay, western blotting) weredetermined in streptozotocin-diabetic rats (D) with differentlevels of glycemic control (blood glucose 22.0±1.0, 13.4±1.5,8.1±0.4 mmol/l, p<0.05 between the groups), achieved byvarying insulin treatment (0, 4 and 12 IU/day), and in controlrats with (C4) or without (C) chronic insulin administration. RenalAkt activity was reduced in D rats without insulin treatment andsevere hyperglycemia (D-0, -62 %, p<0.01 vs. C), partiallyrestored in moderately hyperglycemic rats (D-4, -30 %, p<0.05vs. C), and normalized in D rats with intensive insulin and tightmetabolic control (D-12). Expression of active mTOR paralleledAkt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D12 that demonstrated increases in active mTOR (+55 %, +80 %resp., p<0.05) as compared to C. Moreover, insulin activatedrenal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion,glycemic control and intensity of insulin treatment are importantmodulators of renal Akt and mTOR activity in diabetes. While Aktactivity is reversible by tight metabolic control, combination ofhyperglycemia and insulin treatment resulted in enhancement ofmTOR activity. In addition to Akt, other signaling pathways likelycontribute to regulation of renal mTOR activity in diabetes.