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

Abstract

This study was performed to test whether the inhibitory effect of elevated D-glucose concentrations on insulin-stimulated chemokinesis in normal human neutrophils is mediated by increase in protein kinase C (PKC) activity. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) at 0-100 nM dose-dependently inhibited neutrophil random locomotion in the absence of insulin. Suboptimal concentrations of PMA (0.1-0.5 nM) inhibited the chemokinetic effect of 160 U/mL insulin in a dose-dependent way. The specific PKC inhibitor bisindolylmaleimide (GF 109203x) did not affect the insulin-stimulated chemokinesis at 5 mM glucose but restored the chemokinetic effect of insulin at 15 mM glucose. These results therefore suggest that glucose-induced PKC activation may mediate the inhibitory effects of high glucose levels on insulin-stimulated chemokinesis in normal human neutrophils. J. Leukoc. Biol. 65: 635-640; 1999.

Insulin inhibits phagocytosis in normal human neutrophils via PKCα/β-dependent priming of F-actin assembly

“…Values are mean±SEM for 3-6 separate experiments. man neutrophils [16], reversed the inhibitory effect of insulin on neutrophil phagocytosis to the same extent as that seen for Go6976 (Fig. 6B), suggesting that PKD is not involved in this mechanism.…”

“…Phagocytosis was quantifi ed by fl ow cytometry, as described in materials and methods, and is expressed as per cent of that in the control. The concentrations of the inhibitors were chosen as being optimal for inhibition in other systems [13,16]. *P < 0.05 and **P < 0.01, as compared with that without insulin in the same group, using Student's t-test for paired comparisons.…”

Hyperglycemia in the Intensive Care Unit: No Longer Just a Marker of Illness Severity

“…These studies, as well as the landmark study by Van den Berghe et al, which comprised mostly cardiac surgery patients, suggest that hyperglycemia may not be simply a marker of disease/injury and its severity, but an independent risk factor for mortality [4]. The observed increase in mortality has been ascribed to an increased risk of nosocomial infection and organ failure due to the multifactorial effects of hyperglycemia on suppressing immune function [4,[19][20][21][22][23]. Despite this convincing evidence, it can be argued that some amount of hyperglycemia may be necessary and beneficial, as increasing glucose availability to insulin-insensitive tissues in times of physiologic stress would seem advantageous.…”

Effects of insulin on N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated production of reactive oxygen metabolites from normal human neutrophils

“…This suggests that at least two fundamental steps in the transmission of the insulin signal, found in other cell types [38], is important also for the effect of insulin in neutrophils [16]. Furthermore, in accord with the opinion that the ability of insulin to activate PKC is questionable [39], it was shown that inhibition of PKC did not affect the chemokinetic properties of insulin [15,40]. Also, the initial fMet-Leu-Phe-induced peak of luminolenhanced chemiluminescence was reported to occur independent of PKC-activation [41].…”