Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.
J Immunol
; 199(10): 3634-3643, 2017 11 15.
Article
em En
| MEDLINE
| ID: mdl-29038248
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Salmonella
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Salmonella typhimurium
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Sepse
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Hiperinsulinismo Congênito
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Insulina
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2017
Tipo de documento:
Article