Hypoglycemia and LPS

There is a connection between hypoglycemia and LPS, a very common bacterial toxin. A research article states:
"It is also well known that LPS induces hypoglycemia in experimental animals as well as in humans " [1].

Research article about LPS and hypoglycemia.

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1: Clin Diagn Lab Immunol. 2002 Nov;9(6):1307-12. Primary role of interleukin-1 alpha and interleukin-1 beta in lipopolysaccharide-induced hypoglycemia in mice.

Oguri S, Motegi K, Iwakura Y, Endo Y.

Departments of Pharmacology. Maxillofacial and Plastic Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-Machi, Aoba-Ku, Sendai 980-8575, Japan.

Within a few hours of its injection into mice, lipopolysaccharide (LPS) induces hypoglycemia and the production of various cytokines. We previously found that interleukin-1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) induce hypoglycemia and that the minimum effective dose of IL-1 alpha or IL-1 beta is about 1/1000 that of TNF-alpha. In the present study, we examined the contribution made by IL-1 to the hypoglycemic action of LPS. Nine other cytokines tested were all inactive at inducing hypoglycemia. LPS produced hypoglycemia in mice deficient in either IL-1 alpha or IL-1 beta but not in mice deficient in both cytokines (IL-1 alpha and -1 beta knockout [IL-1 alpha/beta KO] mice). IL-1 alpha, IL-1 beta, and TNF-alpha induced hypoglycemia in IL-1 alpha/beta KO mice, as they did in normal control mice. The LPS-induced elevation of serum cortisol was weaker in IL-1 alpha/beta KO mice than in control mice, and, in the latter, serum cortisol was markedly raised while blood glucose was declining. IL-1 alpha decreased blood glucose both in NOD mice (which have impaired insulin production) and in KK-Ay mice (insulin resistant). These results suggest that (i). cortisol may not be involved in mediating the resistance of IL-1 alpha/beta KO mice to the hypoglycemic action of LPS, (ii). as a mediator, IL-1 is a prerequisite for the hypoglycemic action of LPS, (iii). IL-1 alpha and IL-1 beta perform mutual compensation, and (iv). IL-1 plays a role as the primary stimulator of the many anabolic reactions required for the elaboration of immune responses against infection.

PMID: 12414765 [PubMed - indexed for MEDLINE]

PMCID: PMC130127

1: Br J Pharmacol. 1984 Apr;81(4):645-50.

Induction of hypoglycaemia and accumulation of 5-hydroxytryptamine in the liver after the injection of mitogenic substances into mice.

Endo Y.

Various mitogenic substances (concanavalin A, pokeweed mitogen, polyI : polyC and a phorbol diester), as well as lipopolysaccharides (LPS or endotoxins), produced hypoglycaemia after being injected into mice. However, non-mitogenic immuno-stimulants (zymosan, carrageenan, an adjuvant peptide and interferon) did not induce hypoglycaemia. All of the mitogenic substances also induced an increase in 5-hydroxytryptamine (5-HT) in liver, but the non-mitogenic substances did not have this effect. The time course of the development of hypoglycaemia was similar to that of the increase in liver 5-HT. The dose-dependence of the hypoglycaemia induced by LPS was similar to that of the increase in liver 5-HT. In C3H/HeJ mice, the macrophages and/or lymphocytes of the mice are known to be less responsive to LPS, and both the LPS-induced hypoglycaemia and increase in 5-HT were less in these mice than in control mice (C3H/He and ddI mice). These results suggest that macrophages and/or lymphocytes may participate in the induction of hypoglycaemia and the increase in 5-HT induced by mitogenic substances and LPS. A possible correlation between hypoglycaemia and the increase in hepatic 5-HT is discussed, although the relationship is not substantiated.

PMID: 6722393 [PubMed - indexed for MEDLINE]

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1: Acta Hepatogastroenterol (Stuttg). 1977 Apr;24(2):64-81.

Significance of endotoxaemia in experimental "galactosamine-hepatitis" in the rat.

Grun M, Liehr H, Rasenack U.

The course of galactosamine hepatitis induced by 1.0 g/kg i.p. injected galactosamine (Ga1N) was investigated a sequential study in normal rats, in colectomized rats, and in rats being endotoxin resistent against both exogenous and endogenous endotoxin. Clinical symptoms of Ga1N-hepatitis such as pyrogen reaction, disseminated intravascular coagulation, arterial hypotension, and hypoglycaemia correlated significantly with the development of endotoxaemia, which was detected by means of the limulus gelation test (L.G.T.) Ga1N refractoriness was found after colectomy, a situation, in which gram negative bacterias and their endotoxins were eliminated. Ga1N refractoriness was also observed in case of endotoxin resistence. It is concluded that endotoxins contribute significantly to the pathogenesis of "Ga1N-hepatitis" and its clinical symptoms.

[1] Click here to view this article on PubMed

"It is also well known that LPS induces hypoglycemia in experimental animals as well as in humans."

Inside the first paragraph after the abstract