Hyperglycaemia increases the risk of developing diabetic nephropathy, with primary targets in the glomerulus and proximal tubule. Importantly, glomerular damage in the kidney leads to elevated albumin levels in the filtrate, which contributes to tubular structural modifications that leads to dysfunction. Diabetes alters the endocannabinoid system in a number of target organs, with previous research characterising tissue-specific changes in the expression of the cannabinoid receptor 1 (CB1 ) and putative cannabinoid receptor, GPR55, in diabetes. Despite a functional role for the cannabinoid system in the kidney, there has been little investigation into changes in the expression of CB1 and GPR55 in the proximal tubule under diabetic conditions. CB1 and GPR55 mRNA and protein levels were quantified in cultured human kidney (HK2) cells, treated with either elevated glucose or albumin in isolation and in combination, for a period of 4, 6, 18 or 24 hours. In addition, CB1 and GPR55 protein expression was characterized in whole kidney lysate from streptozotocin (STZ) induced diabetic Sprague Dawley rats. In vitro, exposure to elevated glucose and albumin increased both CB1 and GPR55 mRNA and protein expression in proximal tubule cells in a time-dependant manner. In whole kidney of STZ-induced diabetic rats, CB1 protein was upregulated, whereas GPR55 protein concentration was not altered. Thus, expression of CB1 and GPR55 in proximal tubules is altered in response to exposure to elevated levels of glucose and albumin. Further investigations should determine if these receptors are effective physiological targets for the treatment and prevention of diabetic nephropathy. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.