Altered Postreceptor Signal Transduction of Formyl-Met-Leu-Phe Receptors in Polymorphonuclear Leukocytes of Patients with Non-Insulin-Dependent Diabetes Mellitus

Impaired neutrophil store‐mediated calcium entry in Type 2 diabetes

“…The demonstration of increased [Ca 2+ ] i in resting neutrophils from patients with Type 2 diabetes is consistent with previous findings in neutrophils [11] and other tissues [28,29]. Increased resting [Ca 2+ ] i may be owing to reduced activity of membrane Ca 2+ -ATPase activity in Type 2 diabetes [30].…”

“…Previous work has shown that incubation of neutrophils, from healthy controls, with 10 nmol L −1 fMLP is associated with a significant increase in [Ca 2+ ] i and that this can occur when cells are incubated in calcium-free medium [28]. The fact that we were able to show a significantly lower increase in [Ca 2+ ] i in response to fMLP in the absence of extracellular calcium supports the hypothesis that the process being studied here is that of store-mediated calcium entry, rather than release of calcium from intracellular stores.…”

Crosstalk of sterol‐dependent and non‐sterol‐dependent signaling in human monocytes after in vitro addition of LDL

“…[5][6][7][8] It should be pointed out that the level of IP 3 , [Ca 2þ ]i, and membrane-bound PKC activity in resting monocytes are in reasonable agreement with those already found both in the literature and our earlier work. [10][11][12] In our present study, LDL induced the IP3 and Ca 2þ signals and PKC activation and translocation into the membrane in human monocytes. The PKC activation in the membrane fraction was inhibited by PT and H-7, suggesting that PKC activation depends on the IP 3 and Ca 2þ signal.…”

“…9 In our earlier publications, it was demonstrated that neutrophils of patients with hypercholesterolemia are characterized by increased membrane-bound PKC activity and by decreased signal processing through chemotactic peptide receptors such as FMLP and angiotensin II. [10][11][12] Consequently, if it is true that LDL-Rs have a dual signaling system, and this system is involved in the regulation of intracellular cholesterol homeostasis, then clarification of LDL-R signaling may produce very significant data to help the better understanding of the pathomechanism of atherosclerosis.…”

Hyperglycemia in vitro attenuates insulin-stimulated chemokinesis in normal human neutrophils. Role of protein kinase C activation

“…Also, in neutrophils PMA-stimulated respiratory burst has been shown to be unaffected by increased glucose concentrations [33][34][35]. Recently, however, unstimulated neutrophils from type 2 diabetics were also found to have an increased membrane-bound PKC activity [36]. The increased membrane-bound PKC activity in endothelial cells in the presence of increased glucose concentrations was suggested to be mediated by de novo synthesis of diacylglycerol from glucose [37].…”