Korean J Physiol Pharmacol.  2016 Jan;20(1):83-89. 10.4196/kjpp.2016.20.1.83.

Effect of D-glucose feeding on mortality induced by sepsis

• Kim SS
• Sim YB
• Park SH
• Lee JR
• Sharma N
• Suh HW

• KMID: 2150477
• DOI: http://doi.org/10.4196/kjpp.2016.20.1.83

Abstract

Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 microg/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality.

Keyword

Blood glucose; D-glucose; PTX-sensitive G-proteins; Sepsis-mortality; Spinal cord

MeSH Terms

Animals
Blood Glucose
Glucose*
GTP-Binding Proteins
Hyperglycemia
Mice
Mice, Inbred ICR
Mortality*
Pertussis Toxin
Sepsis*
Spinal Cord
Blood Glucose
GTP-Binding Proteins
Glucose
Pertussis Toxin

Figure

• 

  Fig. 1 Dose-dependent effects of D-glucose on mortality and hypoglycemia induced by sepsis.Mice were orally fed with various amounts (from 1 to 8 g/kg) with D-glucose 30 min prior to i.p. administration with GaLN (0.6 g/10 ml)/LPS (27 µg/27 µl). (A) The mortality rate was measured at 12, 24, 36, 48, 72, 84 and 96 h after GaLN/LPS injection. (B) The blood glucose level was measured in sepsis mice model after various doses of D-glucose (1~8 g/kg) at 30 min, 1 h, 3 h and 6 h. The number of animals used for each group was 10 (***p < 0.001; compared to sepsis group, **p<0.01; compared to sepsis group).

• 

  Fig. 2 Effect of D-glucose post-treated orally on sepsis-induced mortality.The mice were orally fed with D-glucose (8 g/kg) at 1 (A), 3 (B), 6 (C), 9 (D) and 12 (E) h after i.p. administration with GaLN (0.6 g/10 ml)/LPS (27 µg/27 µl). The mortality rate was counted at 12, 24, 36, 48, 72, 84 and 96 h after GaLN/LPS injection. The number of animals used for each group was 10.

• 

  Fig. 3 Effect of D-glucose post-treated orally on sepsis-induced hypoglycemia.The mice were orally fed with either D-glucose (8 g/kg) at 1 (A), 3 (B), 6 (C), 9 (D) and 12 (E) h after i.p. administration with GaLN (0.6 g/10 ml)/LPS (27 µg/27 µl). The blood glucose level was measured at various times after GaLN/LPS injection. The number of animals used for each group was 10. (***p,#x003C;0.001; compared to sepsis group, **p,#x003C; 0.01; compared to sepsis group).

• 

  Fig. 4 Effect of i.t. pretreatment with PTX on D-glucose-induced survival and hyperglycemic effects in sepsis model.Mice were pretreated i.t. once with either saline or PTX (0.1 µg/0.5 µl) once for 6 days and D-glucose (8 g/kg) was orally fed 30 min prior to i.p. administration with GaLN (0.6 g/10 ml)/LPS (27 µg/27 µl). The mortality rate (A) was measured at 12, 24, 36, 48, 72, 84 and 96 h after GaLN/LPS injection. the blood glucose level (B) was measured at various times after GaLN/LPS injection. The number of animals used for each group was 10 (***p,#x003C;0.001; **p,#x003C;0.01; compared to Saline+Saline/sepsis group, +++p,#x003C;0.001; ++p,#x003C;0.01; compared to Saline+D-glucose/sepsis group).

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