Biological Effects of Blood Glucose Level Control
Tatsurou Yagami, Kenkichi Takase, Yasuhiro Yamamoto
Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo, Japan
 
Blood glucose control performed by intensive care unit (ICU) nurses is becoming standard practice for critically ill patients. Hyperglycaemia is associated with increased risk of death in ICU patients. Recent studies on blood-glucose control failed to fully clarify whether this association is causal. In both ICU deaths and post-ICU deaths, sepsis is the leading cause of death. Therefore, we will put the biological effects of blood glucose level control in perspective of sepsis. Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. The toxicity of glucose on the immune system can be associated with the early phase of the innate immune reaction and the cytokine and chemokine networks. Early proinflammatory cytokines e.g. tumor necrosis factor – a (TNF-a) are increased in hyperglycemia. Sepsis is also initially characterized by increases in inflammatory mediators such as TNF-a; but as sepsis persists, there is a shift toward an anti-inflammatory immunosuppressive state. The initial immune response is hyperinflammatory, but the response rapidly progresses to hypoinflammatory. Patients with sepsis have features consistent with immunosuppression, including a loss of delayed hypersensitivity, an inability to clear infection, and a predisposition to nosocomial infections. In the innate immune system, hyperglycemia induces apoptosis of lymphocytes, and impairs chemotactic migration and phagocytosis of polymorphonuclear lymphocytes. Although plasma concentration of complement products are increased under high glucose, complement function are decreased. The administration of interferon-g in patients with sepsis reversed the adverse sequelae of sepsis-induced immunosuppression, and improved survival. This presentation will review how blood glucose level control can be biologically contributed to the reduction of mortality in ICU. Furthermore, we will try to propose a promising treatment from the biological study of glycemic control.

Biography
Dr. Yagami completed his doctorate in biochemistry with the functional analysis of adrenaline receptors regulating the blood glucose level at the Osaka University in 1995. As a post doctorate, he evaluated pharmaceutical compounds for inflammatory diseases such as Stroke and Alzheimer’s disease in Shionogi Research Laboratories. His pharmacological study shed light on the important role of arachidonic acid cascade from secretory phospholipase A2 to prostaglandins in these diseases. In 2003, he was invited as an assistant professor to search receptors for the adrenaline precursor, 3,4-dihydroxyphenylalanine, at the Yokohama City University. His molecular biological study cleared the physiological function of a novel seven-transmembrane receptor in Caenorhabditis elegans. Dr. Yagami was invited as a professor at the Himeji Dokkyo University to study how 15-deoxy-D12,14-prostaglandin J2 (15d-PGJ2) is involved in the inflammation. 15d-PGJ2 is an endogenous carcinostatic cyclopentenone, and binds to a nuclear receptor, peroxysome proliferator-activated receptor ??(PPAR?). He was the first to demonstrate that 15d-PGJ2 induces apoptosis via the specific binding sites of 15d-PGJ2 on the cell surface independent from PPAR?. With a proteomic approach, he identified protein targets for 15d-PGJ2 in the plasma membrane of neurons and cancer cells. Recently, he found that 15d-PGJ2 could modulate glycolytic systems and immune systems. His elucidation of mechanisms for 15d-PGJ2-induced inflammation is expected to a prelude to a new generation of drug treatments for inflammatory diseases.