Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function.
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).


METHODS
Prospective cohort study.


METHODS
A university-county hospital.


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


METHODS
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.


METHODS
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/10(6) PMNLs; P < 0.01); and impaired phagocytosis (117 +/- 21.0 compared with 145 +/- 17.4 micrograms oil/10(7) PMNLs 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 imparied phagocytosis seen in these patients.
D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology*; D011446:Prospective Studies
D007004:Hypoglycemic Agents; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium