Lipopolysaccharide inhibits hepatic gluconeogenesis in rats: The role of immune cells. Issue 3 (13th September 2017)

• Record Type: Journal Article
• Authors: Tanaka, Hiroshi; Nishikawa, Yoshikazu; Fukushima, Toru; Taniguchi, Ataru; Fujita, Yoshihito; Tsuda, Kinsuke; Inagaki, Nobuya; Hosokawa, Masaya
• Is Part Of: Journal of diabetes investigation. Volume 9:Issue 3(2018)
• Page Start: 494
• Page End: 504
• Publication Date: 2017-09-13
• Subjects: Lipopolysaccharide -- Liver -- Spleen; Diabetes -- Periodicals; Diabetes -- Research -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462005
• DOI: 10.1111/jdi.12729
• Languages: English
• ISSNs: 2040-1116

Abstract

Abstract: Aims/Introduction: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis‐induced hypoglycemia has not yet been examined in detail. The aim of the present study was to investigate the mechanisms underlying hypoglycemia in sepsis. Materials and Methods: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test. The effects of LPS on glucose metabolism were investigated in perfused livers and isolated hepatocytes. Furthermore, its effects on the production of inflammatory cytokines were examined in isolated splenocytes. The interaction between splenocytes and hepatocytes in response to LPS was investigated in vitro using a co‐culture of splenocytes and hepatocytes. Results: In the pyruvate tolerance test, the pretreatment with LPS decreased gluconeogenesis. The in vivo pretreatment of rats with LPS did not inhibit glucose production in perfused livers. The in vitro treatment of isolated hepatocytes with LPS did not decrease hepatic gluconeogenesis. Although LPS increased the production of inflammatory cytokines (tumor necrosis factor‐α, interferon‐γ, interleukin‐1β, interleukin‐6 and interleukin‐10) and nitric oxide in isolated splenocytes, only nitric oxide significantly inhibited gluconeogenesis in isolated hepatocytes. When splenocytes and hepatocytes were co‐cultured in medium containing LPS, the messenger ribonucleic acid expression of glucose‐6‐phosphatase in hepatocytes was suppressed. Conclusions: LPS reduced hepatic gluconeogenesis, at least in part, by stimulating the production of nitric oxide in splenocytes. This effect could contribute to the mechanisms responsible for septicemia‐induced hypoglycemia. Abstract : In the pyruvate tolerance test, the pretreatment with LPS decreased gluconeogenesis. When splenocytes and hepatocytes were co‐cultured in medium containing LPS, the mRNA expression of glucose‐6‐phosphatase (G6Pase) in hepatocytes was suppressed.