Effect of acute hyperglycemia and/or hyperinsulinemia on polymorphonuclear functions in healthy subjects

Fejfarová, Vladimı́ra; Jirkovská, Alexandra; Lupínková, Jana; Kovář, J.; Kalanin, J.; Střı́ž, Ilja; Skibová, J; Bouc̆ek, P; Pelikánová, Terezie

doi:10.1016/j.metabol.2006.02.007

Cited by 16 publications

(15 citation statements)

References 38 publications

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“…There exists a close link between glucose metabolism and PMN functions. 5 Neutrophil functions are impaired in patients with diabetes mellitus. 6 Impaired PMN function is regarded as a major cause for infectious complications in diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Phagocytic activity of neutrophils improves over the course of therapy of diabetic foot infections

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et al. 2007

Journal of Infection

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Section: Introductionmentioning

confidence: 99%

Phagocytic activity of neutrophils improves over the course of therapy of diabetic foot infections

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et al. 2007

Journal of Infection

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“…Therefore, neutrophil dysfunction may be involved in the high susceptibility of diabetic patients to staphylococcal infection. However, results remain conflicting and equivocal with regard to neutrophil function in diabetic hosts (3,15,40). Although analyses of neutrophil function among diabetic patients may provide information to enable diabetic patients to more effectively overcome infectious complications, it has yet to be fully elucidated how diabetic hyperglycemia affects the neutrophil-mediated host defense and also how insulin treatment affects diabetes-related infections.…”

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confidence: 99%

Insulin Treatment Directly Restores Neutrophil Phagocytosis and Bactericidal Activity in Diabetic Mice and Thereby Improves Surgical Site Staphylococcus aureus Infection

et al. 2012

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Bacterial infections, including surgical site infections (SSI), are a common and serious complication of diabetes. Staphylococcus aureus, which is eliminated mainly by neutrophils, is a major cause of SSI in diabetic patients. However, the precise mechanisms by which diabetes predisposes to staphylococcal infection are not fully elucidated. The effect of insulin on this infection is also not well understood. We therefore investigated the effect of insulin treatment on SSI and neutrophil function in diabetic mice. S. aureus was inoculated into the abdominal muscle in diabetic db/db and high-fat-diet (HFD)-fed mice with or without insulin treatment. Although the diabetic db/db mice developed SSI, insulin treatment ameliorated the infection. db/db mice had neutrophil dysfunction, such as decreased phagocytosis, superoxide production, and killing activity of S. aureus; however, insulin treatment restored these functions. Ex vivo treatment (coincubation) of neutrophils with insulin and euglycemic control by phlorizin suggest that insulin may directly activate neutrophil phagocytic and bactericidal activity independently of its euglycemic effect. However, insulin may indirectly restore superoxide production by neutrophils through its euglycemic effect. HFD-fed mice with mild hyperglycemia also developed more severe SSI by S. aureus than control mice and had impaired neutrophil phagocytic and bactericidal activity, which was improved by insulin treatment. Unlike db/db mice, in HFD mice, superoxide production was increased in neutrophils and subsequently suppressed by insulin treatment. Glycemic control by insulin also normalized the neutrophil superoxide-producing capability in HFD mice. Thus, insulin may restore neutrophil phagocytosis and bactericidal activity, thereby ameliorating SSI.T he number of patients with diabetes mellitus has increased greatly worldwide (8,48). It is well known that diabetic patients are more prone to bacterial infections, including surgical site infections (SSI), than healthy individuals. Although many clinical reports have demonstrated that glycemic control reduces the risk of infections, the precise mechanisms by which diabetes predisposes to infections are not well understood (2, 21, 38). Control of bacterial infections has become more important for diabetic patients than in the past, because of the increase in diabetic patients and their susceptibility to infections. Foot infections following skin ulceration are also common causes of hospitalization for diabetic patients (6). These infectious complications seriously impair prognoses for diabetic patients (44).Gram-positive bacteria cause more than half of cases of diabetesrelated wound infections. Especially, Staphylococcus aureus is a major pathogen in these infections (44). Methicillin-resistant S. aureus (MRSA) also has become prevalent among both nosocomial and community-acquired infections in diabetic patients (44). Neutrophils play crucial roles in eliminating bacteria, including S. aureus, from hosts (22). Therefore, neutrophil ...

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“…The in vitro inhibitory effect of glucose on the oxidative metabolism of canine neutrophils has also been observed in humans in vivo [9]; however, some studies did not find alterations in the oxidative metabolism of diabetic patients [10,11], while others found increased oxidative metabolism [8,5-7]. This discrepancy among the results of studies that evaluated neutrophil oxidative metabolism may be due to the heterogeneity of their protocols; different concentrations of glucose were used, various stimuli were used to activate the cells, and oxidative metabolism was assessed by different methods [3].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have reported increased ROS production in diabetic patients [5-7], and in healthy patients that underwent a hyperglycemic challenge [8]. The reduction of the neutrophil oxidative burst in patients with poorly controlled diabetes mellitus has also been described [9], but such alteration did not occur in patients with experimentally varied concentrations of blood glucose [10] and with acute, induced hyperglycemia [11]. …”

Section: Introductionmentioning

confidence: 99%

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro

et al. 2013

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BackgroundDogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs.ResultsThe capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate.ConclusionsA high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions.

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Effect of acute hyperglycemia and/or hyperinsulinemia on polymorphonuclear functions in healthy subjects

Cited by 16 publications

References 38 publications

Phagocytic activity of neutrophils improves over the course of therapy of diabetic foot infections

Phagocytic activity of neutrophils improves over the course of therapy of diabetic foot infections

Insulin Treatment Directly Restores Neutrophil Phagocytosis and Bactericidal Activity in Diabetic Mice and Thereby Improves Surgical Site Staphylococcus aureus Infection

High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro

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