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 common diseases which are independently associated with insulin resistance/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 [Ca2+]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 concentration-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 response 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) platelet [Ca2+]i. Thus, an enhanced platelet [Ca2+]i response to LDL is characteristic of diabetes, independently of blood pressure. As such, it may also help to explain the enhanced platelet aggregation, endothelial dysfunction, and accelerated atherosclerosis of NIDDM.