Intracellular calcium handling by fibroblasts from non-insulin dependent diabetic patients with and without hypertension and microalbuminuria

Abstract

Intracellular calcium ([(Ca2+(i)]) plays a role in many cellular functions, and is involved in the pathogenesis of some conditions observed in non-insulin dependent diabetic patients (NIDDM), such as hypertension and insulin resistance. Hyperinsulinemia and hyperglycemia are also implicated in the pathogenesis of chronic diabetes complications. It is not clear whether disturbances in [(Ca2+)(i)] are accounted for only by metabolic abnormalities of diabetes or by other mechanisms. The aim of this study was to investigate [(Ca2+)(i)] handling by skin fibroblasts in NIDDM patients with similar features regarding diabetes duration and metabolic control, but who differ concerning blood pressure levels and albumin excretion rate. Using a fluorimetric technique with the indicator Fura-2/AM, we investigated the effect of chronic exposure to insulin and glucose on [(Ca2+)(i)] after FGF stimulation in fibroblasts from NIDDM with hypertension alone (NIDDM H+M-) and with hypertension and microalbuminuria (NIDDM H+M+) in comparison with normotensive normoalbuminuric (NIDDM H+M+) and control subjects (C). We studied also a group of hypertensive non-diabetic subjects (HYPER). We found that (1) FGF increases [(Ca2+)(i)] in all subjects; (2) insulin or high glucose per se increase [(Ca2+)(i)] in NIDDM H+M+ and NIDDM H+M- with respect to NIDDM H-M and C; (3) HYPER show a [(Ca2+)(i)] response similar to that of NIDDM H+M- and NIDDM H+M+; (4) when stimuli are combined, all NIDDM have altered {(Ca2+)(i)] with respect to C, but NIDDM H+M-. NIDDM H+M+ and HYPER have higher values than NIDDM H-M-. This disorder in {(Ca2+)(i)] appears to be an intrinsic feature of a subgroup of hypertensive NIDDM patients, which persists in cultured cells, at least partially independent of the metabolic challenge of diabetes in vivo, and could contribute to the development of their renal and cardiovascular complications.