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Title: SGK and disrupted renal sodium handling in diabetes
Author: Hills, Claire Elizabeth
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2006
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Diabetic nephropathy is associated with secondary hypertension arising from aberrant sodium reabsorption in the kidney. This thesis characterises a novel human cell line derived from the human cortical collecting duct (HCD) to assess glucoseevoked changes in key elements, such as the serum and glucocorticoid inducible kinase (SGKI) and the epithelial sodium channel (ENaC), involved in the regulation of sodium transport. In addition I have also examined the effects of TGF-f3I and [Ci+]i on SGKI and ENaC expression. RT-PCR, western blot analysis, immunocytochemistry and single cell imaging were employed to determine presence, localisation and function of these elements under various glycaemic conditions. Our data suggest that high glucose, TGF-f3I and [Cl+]i up-regulate both SGKI and [alpha]ENaC protein expression, which in turn stimulates Na+ transport. In pathological conditions associated with aberrant Na + reabsorption, excessive levels of Na + may further exacerbate the state of hypertrophy, a common manifestation associated with diabetic nephropathy. Mechanical stress evoked TRPV4 m~diated changes in [Ca2+]i. Propagation of this Ca2+ signal via the gap junction protein connexin 43 (Cx-43) was enhanced following glucose treatment, as was Cx-43 expression. Under pathophysiological conditions these changes and the increased expression levels of our key signaling elements, may lead to deranged Na+ handling and inhibition of cell volume recovery mechanisms which together may further enhance the condition of diabetic nephropathy in Type 11 diabetes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QM Human anatomy