The platelet angiotensin II receptor in type I diabetes: studies in patients with and without nephropathy

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Abstract
Experimental studies demonstrate impaired regulation of the mesangial angiotensin II (AII) receptor in diabetes. This could contribute to the disturbance of glomerular blood flow and the development of diabetic nephropathy. The aim of this study was to determine whether a similar receptor abnormality occurs in patients with type I insulin‐dependent diabetes mellitus (IDDM) and if so whether this is more prevalent in patients with micro‐ or macro‐albumi‐nuria. The platelet AII receptor was chosen because of its availability from the circulation and its comparable regulatory properties to tissue‐based receptors. The interaction between plasma All and its platelet receptor was examined in 45 patients with TDDM and 36 age‐ and sex‐matched control subjects. Seven patients had clinical nephropathy and two had persistent micro‐albuminuria. The duration of diabetes varied from 1 month to 42 years.There was a significant inverse correlation between plasma AIT and the logarithm of receptor number in the control group (r= ‐0.555, P P <0.05). Patients without nephropathy had a significantly lower receptor number than control subjects (i.e. 3.9 ± 0.4 and 5.1±0.7 sites per cell respectively; P = 0.02), while comparable values to controls were observed in patients with renal disease (5.7 ±1.2 sites per cell). Plasma renin and AII levels for both groups of patients were comparable to those observed in the control subjects.If these findings are representative of tissue‐based AII receptors, then the loss of ligand/receptor relationship in the presence of higher receptor expression in patients with nephropathy could provide an explanation for the glomerular haemodynamic abnormalities observed in human diabetes.

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