Elevated cytosolic calcium and impaired proliferation of B lymphocytes in type II diabetes mellitus.
Patients with diabetes mellitus have increased susceptibility to infection attributable, at least in part, to defective function of polymorphonuclear leukocytes (PMNLs) and B cells. Certain data suggest that cytosolic calcium ([Ca2+]i) is elevated in various cells in diabetes, and high [Ca2+]i adversely affects cell function. Indeed, the [Ca2+]i of PMNLs of diabetic patients is elevated, and phagocytosis of the PMNLs is impaired. The current study examines whether the [Ca2+]i of B cells is also elevated in diabetes and whether this derangement impairs B cell function. We studied 32 patients with non-insulin-dependent diabetes mellitus (NIDDM) and eight normal subjects. All patients had hyperglycemia (11.6 +/- 0.80 mmol/L) and elevated HbA1c (13.2% +/- 0.99%). The basal levels of [Ca2+]i of the B cells (113 +/- 3.3 nmol/L) were significantly (P < 0.01) higher than the values in normal subjects (85 +/- 1.7 nmol/L). There was a direct and significant correlation (r = 0.88; P < 0.01) between the [Ca2+]i of B cells and the blood levels of glucose. Proliferation of B cells in response to Staphylococcus aureus Cowan I (SAC) was significantly impaired in these patients (7.3 +/- 0.48 x 10(3) cpm v 12.5 +/- 0.61 x 10(3) cpm in normal subjects). Normalization of blood glucose with the hypoglycemic agents, glyburide, was associated with the return of both [Ca2+]i of B cells and their proliferation in response to SAC to normal. The results show that hyperglycemia in type II diabetes mellitus is associated with a significant increase in [Ca2+]i of B cells and with a decrease in their proliferation in response to mitogen. These derangements are reversed after the correction of the hyperglycemia. The data of the current study and those previously reported in PMNLs provide for a new pathogenetic process underlying the dysfunction of these cells in diabetes mellitus.
Alexiewicz
J M
JM
Department of Medicine, the University of Southern California, School of Medicine, Los Angeles 90033, USA.
Kumar
D
D
Smogorzewski
M
M
Massry
S G
SG
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division; D003600:Cytosol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000145:classification
D001786:Blood Glucose; D002118:Calcium