In vivo evidences that insulin regulates human polymorphonuclear neutrophil functions

Abstract

Polymorphonuclear neutrophils (PMN) are able to destroy invasive mircoorganisms by a wide variety of functions. Whereas insulin does not stimulate hexose transport in PMN, previous reports have clearly shown that this hormone regulates glucose metabolism inside this cell, raising the question of insulin action on PMN functions in humans. It is interesting that in vitro studies established a strong relationship between specific binding of insulin to its PMN membrane receptor and the activation of the main PMN functions. Therefore, investigation in healthy subjects under strict euglycemia and physiological insulinemia was performed to understand the in vivo-specific action of insulin on PMN functions without hyperglycemia interferences. We determined numerous PMN functions before and after hyperinsulinemia (0.5 mU/kg/min) and euglycemia (0.9 g/l) clamp for 4 h in eight adult healthy volunteers (24+/-6 years). The total number of PMN and the number of PMN expressing CD11b, CD15, CD62L, and CD89 were significantly increased over baseline (P<0.001), whereas the density of these receptors was down-regulated (P<0.01) by insulin. PMN chemotaxis (+117%, P<0.05), phagocytosis (+29%, P<0.001), and bactericidal (+17-25%, P<0.001) capacities were increased during the insulin clamp (P<0.05). Therefore, insulin treatment may modulate PMN functions not only by attainment of a better metabolic control, as suggested by in vivo studies in diabetic patients, but also through a direct effect of insulin.

Common infections in diabetes: pathogenesis, management and relationship to glycaemic control

“…Similar results have been reported for monocytes from diabetic patients [13]. In a more recent study, hyperinsulinaemia in the presence of euglycaemia significantly improved PMN chemotaxis, raising important questions about the direct role of insulin in the immunity of diabetes [14].…”

“…Initial evidence for reduced phagocytosis of opsonized Staphylococcus aureus [6,15] and pneumococcus [5] by PMNs from diabetic subjects has not been confirmed by more recent investigations using the opsonized latex bead ingestion test [7] or other bacteria and fungi [16,17]. As with chemotaxis, PMN phagocytosis has recently been shown to improve in the presence of hyperinsulinaemic euglycaemia [14], adding support to the suggestion that insulin is an important influence on PMN function.…”

Endophthalmitis

“…These important cells are impaired in diabetics. PMN defects in chemotaxis, phagocytosis, and bactericidal activity have been reported in the context of diabetes (Delamaire et al, 1997;Walrand et al, 2004) and PMN from diabetic mice and humans are incapable of phagocytizing and killing both S. aureus and K. pneumoniae (Lin et al, 2006;Park et al, 2009). These defects in the ability of PMNs to clear bacteria that are destined to cross a compromised blood retinal barrier may also contribute to the development and pathogenesis of EE, but this has not been scientifically analyzed.…”

The Role of Insulin in Wound Healing Process: Mechanism of Action and Pharmaceutical Applications

“…Insulin signalling pathways are summarised in Figure 2, which shows the effect of insulin on cellular and molecular mechanisms involved in wound repair. Other proposed mechanisms of action for insulin in wound healing exist, such as the enhancement of expression of neutrophil adhesion molecules to reinforce the cellular functions of migration, phagocytosis and bactericidal actions [33]. Although neutrophils act as traumatic scavengers and help wound healing in some ways, neutrophils also have a negative impact on 4/6 wound healing, particularly when excess or hyper-functional neutrophils accumulate in the wound environment.…”