INCREASED INTRACELLULAR CALCIUM AND ALTERED PHORBOL DIBUTYRATE BINDING TO INTACT PLATELETS IN YOUNG SUBJECTS WITH INSULIN-DEPENDENT AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) a nd non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (13 5 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 s econds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was sign ificantly higher than that of the controls (347 +/- 22 nmol/L, P = .00 3) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM gr oup was significantly lower than that in the control group either unde r basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lowe r than that in the controls only after stimulation with thrombin (P = .047). The K-d for PdBu of the IDDM group was lower than that of the c ontrol group under basal conditions (P = .017). When analyzing the poo led data of all subjects, a significant correlation was observed betwe en Bmax and K-d (under basal conditions, r = .544, P < .0001; after st imulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the b inding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mel litus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients. Copyright (C ) 1997 by W.B. Saunders Company.