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ARTICLE

Polymorphonuclear Leukocytes in Non-Insulin-dependent Diabetes Mellitus: Abnormalities in Metabolism and Function

right arrow Jadwiga M. Alexiewicz, MD; Dinesh Kumar, MD; Miroslaw Smogorzewski, MD; Mariusz Klin, MD; and Shaul G. Massry, MD

15 December 1995 | Volume 123 Issue 12 | Pages 919-924

Objective: To determine basal levels of cytosolic calcium ([Ca2+]i) and phagocytic activity in polymorphonuclear leukocytes (PMNLs) from patients with non-insulin-dependent diabetes (NIDDM).

Design: Prospective cohort study.

Setting: A university-county hospital.

Measurements: Cytosolic calcium levels, adenosine triphosphate (ATP) content, and phagocytosis of PMNLs from patients with NIDDM and from controls.

Intervention: In patients with NIDDM, we evaluated the effect of treatment with an oral hypoglycemic agent (glyburide) on [Ca2+]i levels, ATP content, and the phagocytosis of PMNLs.

Patients: 22 controls and 34 patients with NIDDM were examined. Fifteen patients were studied before and after 3 months of treatment with glyburide.

Results: Polymorphonuclear leukocytes from patients with NIDDM showed significantly elevated basal levels of [Ca2+]i (68 ± 9.6 compared with 43 ± 4.9 nmol/L; P < 0.01); reduced ATP content (1.30 ± 0.58 compared with 2.35 ± 0.45 nmol/106PMNLs; P < 0.01); and impaired phagocytosis (117 ± 21.0 compared with 145 ± 17.4 µg oil/107PMNLs per minute; P < 0.01) compared with controls. There was a direct and significant correlation (P < 0.01, r = 0.80) between [Ca2+]i levels in PMNLs and serum glucose levels and an inverse correlation between phagocytic ability and [Ca2+]i levels (P < 0.01; r = 0.62) as well as between phagocytic activity and fasting serum glucose levels (P < 0.01, r = 0.54) in patients with NIDDM. Glyburide therapy resulted in significant reduction in fasting serum glucose levels; in PMNLs, this treatment resulted in a significant reduction in [Ca2+]i levels, a significant increase in ATP content, and a significant improvement of phagocytosis.

Conclusions: Patients with NIDDM have elevated [Ca2+]i levels in PMNLs. This abnormality is probably induced by hyperglycemia and is primarily responsible for the impaired phagocytosis seen in these patients.

Author and Article Information
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From the University of Southern California School of Medicine, Los Angeles, California.
Grant Support: By National Institute of Diabetes and Digestive and Kidney Diseases grant DK 29955. Dr. Klin was supported by the Fogarty International Fellowship.
Request for Reprints: Shaul G. Massry, MD, Chief, Division of Nephrology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033.
Current Author Addresses: Drs. Alexiewicz, Smogorzewski, Klin, and Massry: Division of Nephrology, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033.
Dr. Kumar: Division of Endocrinology, Diabetes and Hypertension, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033.


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Normalization of Intracellular Calcium: A Sweet Solution to Neutrophil Dysfunction in Diabetes?
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Annals 1995 123: 952-954. [Full Text]  



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