Amlodipine reverses the elevation in [Ca2+]i and the impairment of phagocytosis in PMNLs of NIDDM patients

Abstract

Patients with diabetes mellitus display an elevation in the basal levels of [Ca2+]i of polymorphonuclear leukocytes (PMNLs) and impaired phagocytosis. These derangements are due to the hyperglycemia of diabetes. Calcium channel blockers reverse these abnormalities both in in vitro studies and in diabetic rats. These observations suggest that calcium channel blockers may be useful in the treatment of patients with uncontrolled diabetes. The present study examined this issue. A total of 32 normal subjects and 36 patients with uncontrolled noninsulin-dependent diabetes mellitus (NIDDM) were studied with and without treatment with amlodipine both in a cross-sectional and longitudinal design approach. In addition to the elevation in basal levels of [Ca2+]i and the impaired phagocytosis, there was also down-regulation of the mRNA of Fc gamma RIII receptors in the PMNLs of the diabetic patients. Treatment of the patients with a small dose of amlodipine (5 mg/day) corrected these abnormalities despite persistent hypoglycemia. This beneficial effect of nifedipine was noted as long as the therapy with the drug was maintained. The results show that the elevation in [Ca2+]i of the PMNLs is associated with down-regulation of the mRNA of their Fc gamma RIII receptors, which is at least, in part, responsible for the impaired phagocytosis. These derangements in the metabolism and function of the PMNLs are most likely responsible for the increased susceptibility of the diabetic patients to infection. Calcium channel blockers may be a beneficial adjunct therapy in patients with uncontrolled diabetes.