Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an in ducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G>C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstr ated lower frequencies of the CC genotype (P=0.005). From th e DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1>10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G>C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequenc ies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G>C polymorphism with the risk of DN., J. A. Hubáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels 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 by varying insulin treatment (0,4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hypergly cemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D- 12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes., J. Ždychová, J. Veselá, L. Kazdová, R. Komers., and Obsahuje bibliografii a bibliografické odkazy