Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hagar, JA; Edin, ML; Lih, FB; Thurlow, LR; Koller, BH; Cairns, BA; Zeldin, DC; Miao, EA

Published Date

  • November 2017

Published In

Volume / Issue

  • 199 / 10

Start / End Page

  • 3634 - 3643

PubMed ID

  • 29038248

Pubmed Central ID

  • 29038248

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1700820

Language

  • eng