Objective: Recently, we reported that long-term intake of a water-soluble extract from culture medium of Ganoderma lucidum mycelia (WER) reduced hyperglycemia and enhanced glucose transporter-4 (GLUT4) translocation to the plasma membrane in skeletal muscles and adipose tissue in KK-A^y mice, a type 2 diabetic animal model with obesity. In the present study, we investigated the effect of WER on hepatic carbohydrate metabolism.
Methods: Female KK-A^y mice were given free access to water and high-fat food containing 0.5% WER for 8 weeks, and blood glucose levels were assessed every week. At the end of the experimental period, the expression and activities of sugar metabolic enzymes in the liver were determined by Real Time RT-PCR and each activity measurement method. Also, the amount of glycogen was measured by anthrone-sulfuric acid method. Furthermore, the expression level of GLUT2 and activation of AMP kinase (AMPK) and glycogen synthase kinase 3β (GSk3β) was also determined by western blot analysis.
Results: The mice with the high-fat ingestion showed a gradual increase in the levels of blood glucose and body weight. In the WER-treated mice, the blood glucose level was suppressed after 2 weeks of intake. The gene expression and enzyme activities of both glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were suppressed, whereas those of glucokinase were increased in the mice with WER intake and pioglitazone administration. The accumulation of glycogen was increased. Moreover the expression of GLUT2 and phosphorylation levels of AMPK and GSk3β were also increased in the mice with WER intake.
Conclusion: These results indicate that WER affects hepatic carbohydrate metabolism, which may derive from the suppression of gluconeogenesis through the modulation of related enzymes and enhancement of glucose uptake, glycolysis and glycogen synthesis.

This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (Pg-LPS) on gingival tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli (Ec-LPS) on IL-6 and TNF-α levels were also analysed. Pg-LPS (1 μg/1 μL) or Ec-LPS (1 or 6 μg/1 μL) was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay (ELISA) revealed that gingival dialysates contained approximately 389 pg·mL⁻¹ of IL-6 basally; basal TNF-α levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-α levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-α were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the gingiva expresses Toll-like receptor (TLR) 2 and TLR4 mRNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-α without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-α in rats.
Animals ; Gingiva ; drug effects ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; administration & dosage ; Male ; Porphyromonas gingivalis ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 2 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. METHODS: The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. RESULTS: A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84). CONCLUSION Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.
Case-Control Studies ; Cerebral Palsy ; epidemiology ; etiology ; Delivery, Obstetric ; statistics & numerical data ; Health Facilities ; statistics & numerical data ; Humans ; Incidence ; Infant, Newborn ; Japan ; epidemiology ; Parturition ; Perinatal Care ; statistics & numerical data ; Retrospective Studies ; Time Factors