INTRACELLULAR CALCIUM HANDLING BY FIBROBLASTS FROM NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH AND WITHOUT HYPERTENSION AND MICROALBUMINURIA

Intracellular calcium ([(Ca2+)(i)]) plays a role in many cellular func tions, and is involved in the pathogenesis of some conditions observed in non-insulin dependent diabetic patients (NIDDM), such as hypertens ion 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 onl y by metabolic abnormalities of diabetes or by other mechanisms. The a im of this study was to investigate [(Ca2+)(i)] handling by skin fibro blasts in NIDDM patients with similar features regarding diabetes dura tion and metabolic control, but who differ concerning blood pressure l evels and albumin excretion ratz. Using a fluorimetric technique with the indicator Fura-2/AM, we investigated the effect of chronic exposur e to insulin and glucose on [(Ca2+)(i)] after FGF stimulation in fibro blasts from NIDDM with hypertension alone (NIDDM H+M-) and with hypert ension and microalbuminuria (NIDDM H+M+) in comparison with normotensi ve normoalbuminuric NIDDM (NIDDM H-M-) and control subjects (C). We st udied also a group of hypertensive non-diabetic subjects (HYPER). We f ound 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 HM- with respect to NIDDM H-M- and C; (3) HYPER show a [(Ca2+)(i)] resp onse similar to that of NIDDM H+M- and NIDDM H+M+; (4) when stimuli ar e 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-. T his disorder in [(Ca2+)(i)] appears to be an intrinsic feature of a su bgroup of hypertensive NIDDM patients, which persists in cultured cell s, at least partially independent of the metabolic challenge of diabet es in vivo, and could contribute to the development of their renal and cardiovascular complications.