Rhythmic daily changes in the Na,K-ATPase activity have been previously described for rat kidney cortex, showing two peaks: at 0900 h and 2100 h, and two valleys: at 1500 h and 0100 h - 0300 h. The oscillations in Na,K-ATPase activity are produced by an inhibitor, which binds the enzyme and is present in the rat blood plasma at valley times and absent or at very low concentrations at peak times. Since it has been demonstrated that active Na+ extrusion from the cells of several tissues depends not only on the Na,K-ATPase but also on the ouabaininsensitive Na-ATPase, we studied the activity of this latter enzyme of several rat tissues, i.e., kidney cortex, small intestine, liver, heart and red blood cells along the day. None of these tissues showed any variation of their Na-ATPase activity along the day. Preincubation of kidney cortex homogenates obtained at 0900 h, with blood plasma drawn at 0900 h and 1500 h, did not modify the Na-ATPase activity. Our results indicate that the Na- ATPase activity does not oscillate along the day. These results are in agreement with the idea that the Na-ATPase could partially compensate the Na+ transport affected by oscillations of the Na,K-ATPase activity.
- MeSH
- cirkadiánní rytmus MeSH
- erytrocyty enzymologie MeSH
- játra enzymologie MeSH
- krysa rodu rattus MeSH
- kůra ledviny enzymologie MeSH
- ouabain MeSH
- potkani Sprague-Dawley metabolismus MeSH
- sodíko-draslíková ATPasa metabolismus MeSH
- srdeční komory enzymologie MeSH
- tenké střevo enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
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 hyperglycemic 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.
- Klíčová slova
- Akt kinase, Diabetic nephropathy, Insulin, Mammalian targetof rapmycin, mTOR,
- MeSH
- diabetes mellitus 1. typu enzymologie farmakoterapie komplikace MeSH
- diabetické nefropatie enzymologie etiologie farmakoterapie MeSH
- experimentální diabetes mellitus enzymologie farmakoterapie komplikace MeSH
- financování organizované MeSH
- fosforylace MeSH
- hypoglykemika terapeutické užití MeSH
- inzulin krev terapeutické užití MeSH
- kinasa 3 glykogensynthasy metabolismus MeSH
- krevní glukóza metabolismus MeSH
- krysa rodu rattus MeSH
- kůra ledviny enzymologie účinky léků MeSH
- proteinkinasy metabolismus MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- signální transdukce MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- aktivace enzymů genetika MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- fyziologický stres enzymologie MeSH
- krysa rodu rattus MeSH
- kůra ledviny enzymologie MeSH
- lidé MeSH
- prekurzory enzymů krev metabolismus MeSH
- renin krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- biotransformace MeSH
- enzymová indukce účinky léků MeSH
- játra enzymologie MeSH
- králíci MeSH
- kůra ledviny enzymologie MeSH
- methyltransferasy biosyntéza metabolismus MeSH
- nemoci jater enzymologie MeSH
- nemoci ledvin enzymologie chemicky indukované MeSH
- organortuťnaté sloučeniny MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH