Acute hyperinsulinemia restrains endotoxin induced systemic inflammatory response - an experimental study in a porcine model

Christensen, Vibeke Brix; Andersen, Steen; Andersen, Rebecca; Mengel, A.; Dyhr, Thomas; Andersen, Niels Trolle; Larsson, Anders; Schmitz, Ole; Ørskov, Hans; Tønnesen, Else

doi:10.1097/00003643-200406002-00001

Cited by 23 publications

(40 citation statements)

References 2 publications

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“…We observed that the EH group had lower IL-6 levels than the control group. In agreement with these findings, insulin administration has been shown to decrease proinflammatory cytokine levels and to increase anti-inflammatory cytokine levels in thermal injury [22] and in rat [23] and pig [24] endotoxemia models. Similarly, Jeschke et al [25] have shown that thermally injured children given insulin to maintain the blood glucose level in a range from 120 to 180 mg/dl had decreased IL-1 ␤ and tumor necrosis factor alpha and increased IL-10 levels as compared with patients who received no insulin.…”

Section: Discussionsupporting

confidence: 68%

Euglycemic Hyperinsulinemia in Severe Sepsis and Septic Shock

Wang²,

Bruhn³

et al. 2006

Eur Surg Res

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Background: Recent studies have suggested that strict glucose control with intensive insulin therapy in critically ill patients may result in better outcomes. Whether this is also true in septic shock has not been determined. In addition, whether it is the insulin administration per se or the glucose control that contributes to the beneficial effects is unclear. We raised the hypothesis that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock due to peritonitis. Materials and Methods: Fourteen anesthetized, mechanically ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight i.p. feces to induce sepsis. Ringer’s lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, the animals were randomized to either an EH group (n = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40–90 mg/dl), and potassium (to maintain the potassium level at 4.0– 5.5 mmol/l) or a control group (n = 7) with no intervention. All animals were studied until their spontaneous death or for 30 h. Results: The EH group received a greater volume of 20% glucose, but blood glucose and potassium concentrations were similar in the two groups. No significant differences were found in hemodynamic variables. The circulating interleukin-6 levels increased in both groups after feces injection, but tended to be lower in the EH group (p < 0.05). The survival times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in the control group; p = 0.73). Conclusions: In this clinically relevant sheep septic shock model, EH decreased blood interleukin-6 concentrations but did not change hemodynamics or improve the outcome.

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Section: Discussionsupporting

confidence: 68%

Euglycemic Hyperinsulinemia in Severe Sepsis and Septic Shock

Wang²,

Bruhn³

et al. 2006

Eur Surg Res

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“…Insulin has been shown to suppress endotoxin induced proinflammatory transcription factors and the genes regulated by them in rats and pigs [25,26]. These effects in endotoxin treated rats and pigs have been shown independent of any changes in glucose concentrations.…”

Section: Anti-inflammatory and Cardioprotective Effects Of Insulin Inmentioning

confidence: 98%

Use of Insulin to Improve Glycemic Control in Diabetes Mellitus

Dandona

Chaudhuri

Ghanim

et al. 2008

Cardiovasc Drugs Ther

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These findings are of great interest as it is possible that the prevention of macrovascular complications in type 2 diabetes may require the use of those glucose lowering drugs which have additional anti-inflammatory effects in addition to the control of comorbid conditions (hypertension and dyslipidemia) associated with this disease. Results of future clinical trials are awaited to confirm the benefits of this approach in the primary and secondary prevention of macrovascular complications in type 2 diabetes.

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“…In animal models, it has been shown that insulin itself has a direct inhibitory effect on the inflammation process. 8,9 However in human studies, it has been suggested that these benefits could be directly attributed to IGC rather than to any pharmacological activity of administered insulin per se. 3,4 Recipients of allogeneic hematopoietic SCT (HSCT), which is the most drastic therapeutic modality in patients with hematological malignancies, often suffer from serious complications including infectious diseases, GVHD and multiple organ failure.…”

Section: Introductionmentioning

confidence: 99%