INCREASED PLATELET CYTOSOLIC CALCIUM RESPONSES TO LOW-DENSITY-LIPOPROTEIN IN TYPE-II DIABETES WITH AND WITHOUT HYPERTENSION

Non-insulin dependent diabetes mellitus (NIDDM) and hypertension are c ommon diseases which are independently associated with insulin resista nce/hyperinsulinemia, dyslysidemia, abnormalities of platelet function , and accelerated atherogenesis. The interaction of these independent risk factors is poorly understood. Recently, low density lipoprotein ( LDL) receptors have been described, in platelets, and LDL elevates [Ca 2+]i in these cells. In this study we have evaluated platelet [Ca2+]i responsiveness to LDL and arginine vasopressin (AVP) in NIDDM patients with (n = 28) and without (n = 13) concomitant hypertension, as well as in normal nondiabetic controls (n = 13). Platelet [Ca2+]i concentra tion-response curves to LDL for both NIDDM and hypertensive NIDDM were shifted significantly to the left when compared to the normotensive, nondiabetic controls. By contrast, no differences were seen in [Ca2+]i responses to 10 mumol/L AVP among any of the groups. To determine the possible role of hyperinsulinemia in this accentuated [Ca2+]i respons e to LDL, we measured basal and LDL-stimulated [Ca2+]i in platelets of normal volunteers after insulin treatment (0-100 mU/mL for 30 and 90 min). Insulin did not alter baseline or LDL-stimulated (150 mg/mL) pla telet [Ca2+]i. Thus, an enhanced platelet [Ca2+]i response to LDL is c haracteristic of diabetes, independently of blood pressure. As such, i t may also help to explain the enhanced platelet aggregation, endothel ial dysfunction, and accelerated atherosclerosis of NIDDM.