Normalization of Intracellular Calcium: A Sweet Solution to Neutrophil Dysfunction in Diabetes?

The diapedesis of the white corpuscles, their migration through the vessel wall into the tissues, is one of the principal means of defense possessed by the animal.As soon as the infective agents have penetrated into the body, a whole army of white corpuscles proceed towards the menaced spot, there entering into a struggle with the microorganisms.… The leukocytes, having arrived at the spot where the intruders are found, seize them after the manner of Amoebae and within their bodies subject them to intracellular digestion.

Ilya I'litch Metchnikoff (1882)

The increased susceptibility of persons with diabetes mellitus to complicated soft-tissue, urinary tract, and lower respiratory tract infections is likely to be at least partially due to deficient polymorphonuclear leukocyte (PMNL) function [1-3]. Independent of acidosis and uremia, PMNLs from patients with diabetes mellitus show impaired adherence [4-6], chemotaxis [7], phagocytosis [8, 9], oxidative activity [10], and bactericidal activity [8-10]. These defects are detectable with fasting blood glucose levels greater than 7.2 mmol/L and within 36 hours of insulin withdrawal [10]. Clinical studies have shown that improved PMNL function accompanies improvement of fasting blood glucose values [3], whereas in vitro studies indicate that such improvement occurs within 15 to 20 minutes of co-incubation with insulin [10]. The PMNL bactericidal defect in patients with diabetes against Staphylococcus aureus[9, 10] may be especially worthy of attention because S. aureus is a frequent and …