The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis.
BACKGROUND
The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis.


METHODS
Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200-300 mg/dL), and no glucose group (100-150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia.


RESULTS
BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at <300 mg/dL. The HG group showed the worst consequences of lung injury and oxidative stress in the liver, which were completely stable in HI group.


CONCLUSIONS
Acute severe hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in the liver.
Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Satoshi
S
Yoneyama
Hideo
H
Terashima
Ryushiro
R
Yamaguchi
Sosuke
S
Tadano
Nobuhiro
N
Ohkohchi
D000208:Acute Disease; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000276:immunology; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D044343:Overnutrition / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000276:immunology* / Q000378:metabolism
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D008315:Malondialdehyde; D005978:Glutathione; D005947:Glucose
Hyperglycemia; Inflammation; Insulin; Metabolic stress; Oxidative stress; Sepsis