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Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.

Publication ,  Journal Article
Hagar, JA; Edin, ML; Lih, FB; Thurlow, LR; Koller, BH; Cairns, BA; Zeldin, DC; Miao, EA
Published in: J Immunol
November 15, 2017

Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81-108 mg/dl) increases the incidence of moderate and severe hypoglycemia, and increases mortality. Septic patients are especially prone to IIT-induced hypoglycemia, but the mechanism remains unknown. Here, we show that codelivery of insulin with otherwise sublethal doses of LPS induced hypoglycemic shock in mice within 1-2 h. LPS impaired clearance of insulin, which amplified insulin receptor signaling. These effects were mediated by caspase-11, TLR4, and complement, each of which trigger eicosanoid production that potentiates insulin signaling. Finally, in an animal model of sepsis, we observed that Salmonella typhimurium-infected mice exhibited simultaneous impaired insulin clearance coexisting with insulin resistance. Our results raise the possibility that septic patients have impaired insulin clearance, which could increase their susceptibility to hypoglycemia during IIT, contraindicating its use.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2017

Volume

199

Issue

10

Start / End Page

3634 / 3643

Location

United States

Related Subject Headings

  • Toll-Like Receptor 4
  • Signal Transduction
  • Sepsis
  • Salmonella typhimurium
  • Salmonella Infections
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lipopolysaccharides
  • Insulin
 

Citation

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Hagar, J. A., Edin, M. L., Lih, F. B., Thurlow, L. R., Koller, B. H., Cairns, B. A., … Miao, E. A. (2017). Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. J Immunol, 199(10), 3634–3643. https://doi.org/10.4049/jimmunol.1700820
Hagar, Jon A., Matthew L. Edin, Fred B. Lih, Lance R. Thurlow, Beverly H. Koller, Bruce A. Cairns, Darryl C. Zeldin, and Edward A. Miao. “Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.J Immunol 199, no. 10 (November 15, 2017): 3634–43. https://doi.org/10.4049/jimmunol.1700820.
Hagar JA, Edin ML, Lih FB, Thurlow LR, Koller BH, Cairns BA, et al. Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. J Immunol. 2017 Nov 15;199(10):3634–43.
Hagar, Jon A., et al. “Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.J Immunol, vol. 199, no. 10, Nov. 2017, pp. 3634–43. Pubmed, doi:10.4049/jimmunol.1700820.
Hagar JA, Edin ML, Lih FB, Thurlow LR, Koller BH, Cairns BA, Zeldin DC, Miao EA. Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. J Immunol. 2017 Nov 15;199(10):3634–3643.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2017

Volume

199

Issue

10

Start / End Page

3634 / 3643

Location

United States

Related Subject Headings

  • Toll-Like Receptor 4
  • Signal Transduction
  • Sepsis
  • Salmonella typhimurium
  • Salmonella Infections
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Lipopolysaccharides
  • Insulin