Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Culturing hepatocytes with a combination of LPS, TNF-alpha, IL-1beta and IFN-gamma resulted in an inhibition of glucose output from glycogen and prevented the repletion of glycogen in freshly cultured cells. The reduced glycogen mobilisation correlated with the lower cell glycogen content and reduced rate of glycogen synthesis from [U-(14)C]glucose rather than alterations in either total phosphorylase or phosphorylase a activity. There was no change in the percentage of glycogen exported as glucose nor the production of lactate plus pyruvate indicating that redistribution of the Gluc-6-P cannot explain the failure of the liver to export glucose. Although changes in glycogen mobilisation correlated with NO production, inhibition of NO synthase by inclusion of L-NMMA in the culture medium failed to prevent the inhibition of either glycogen accumulation or mobilisation by the proinflammatory cytokines, precluding the involvement of NO in this response. LPS plus cytokine treatment had no effect on total glycogen synthase activity although the activity ratio was lowered, indicative of increased phosphorylation. The inhibition of glycogen synthesis correlated with a fall in the intracellular concentrations of Gluc-6-P and UDP-glucose and in the absence of measured changes in kinase activity, it is suggested that the fall in Gluc-6-P reduces both substrate supply and glycogen synthase phosphatase activity. The fall in Gluc-6-P coincided with a reduction in total glucokinase and hexokinase activity within the cells, but no significant change in either the translocation of glucokinase or glucose-6-phosphatase activity. This demonstrates direct cytokine effects on glycogen metabolism independent of changes in glucoregulatory hormones.
 ...
PMID:The control of hepatic glycogen metabolism in an in vitro model of sepsis. 1793 98

Chromogranin A (CHGA/Chga), a proprotein, widely distributed in endocrine and neuroendocrine tissues (not expressed in muscle, liver, and adipose tissues), generates at least four bioactive peptides. One of those peptides, pancreastatin (PST), has been reported to interfere with insulin action. We generated a Chga knock-out (KO) mouse by the targeted deletion of the Chga gene in neuroendocrine tissues. KO mice displayed hypertension, higher plasma catecholamine, and adipokine levels and lower IL-6 and lipid levels compared with wild type mice. Liver glycogen content was elevated, but the nitric oxide (NO) level was diminished. Glucose, insulin, and pyruvate tolerance tests and hyperinsulinemic-euglycemic clamp studies established increased insulin sensitivity in liver but decreased glucose disposal in muscle. Despite higher catecholamine and ketone body levels and muscle insulin resistance, KO mice maintained euglycemia due to increased liver insulin sensitivity. Suppressed mRNA abundance of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (G6Pase) in KO mice further support this conclusion. PST administration in KO mice stimulated phosphoenolpyruvate carboxykinase and G6Pase mRNA abundance and raised the blood glucose level. In liver cells transfected with G6Pase promoter, PST caused transcriptional activation in a protein kinase C (PKC)- and NO synthase-dependent manner. Thus, PST action may be mediated by suppressing IRS1/2-phosphatidylinositol 3-kinase-Akt-FOXO-1 signaling and insulin-induced maturation of SREBP1c by PKC and a high level of NO. The combined effects of conventional PKC and endothelial NO synthase activation by PST can suppress insulin signaling. The rise in blood PST level with age and in diabetes suggests that PST is a negative regulator of insulin sensitivity and glucose homeostasis.
 ...
PMID:A novel pathway of insulin sensitivity in chromogranin A null mice: a crucial role for pancreastatin in glucose homeostasis. 1970 99