INT229276

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Context Info
Confidence 0.54
First Reported 2007
Last Reported 2008
Negated 0
Speculated 1
Reported most in Body
Documents 4
Total Number 13
Disease Relevance 4.56
Pain Relevance 0.51

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

lyase activity (Pck1) nucleus (Pck1) kinase activity (Pck1)
lipid metabolic process (Pck1) cytoplasm (Pck1)
Anatomy Link Frequency
liver 4
hepatocytes 1
Pck1 (Mus musculus)
Pain Link Frequency Relevance Heat
tolerance 93 97.80 Very High Very High Very High
Bile 78 80.84 Quite High
agonist 14 79.92 Quite High
Cholecystokinin 2 56.72 Quite High
anesthesia 11 5.00 Very Low Very Low Very Low
Kinase C 10 5.00 Very Low Very Low Very Low
Immobilon 10 5.00 Very Low Very Low Very Low
imagery 10 5.00 Very Low Very Low Very Low
nud 4 5.00 Very Low Very Low Very Low
Migraine 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Diabetes Mellitus 264 99.28 Very High Very High Very High
Targeted Disruption 100 98.88 Very High Very High Very High
Impaired Glucose Tolerance 52 98.12 Very High Very High Very High
Obesity 88 96.12 Very High Very High Very High
Disorder Of Lipid Metabolism 76 90.88 High High
Insulin Resistance 143 88.68 High High
Repression 12 83.40 Quite High
Lipidosis 30 78.96 Quite High
Hypoglycemia 10 78.84 Quite High
Dyslipidemia /

Combined Dyslipidemia

12 75.00 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Mice with reduced PEPCK-C liver content showed a clear improvement in glucose tolerance and fed glycemia, comparable with the results of oral metformin treatment.
Negative_regulation (reduced) of PEPCK in liver associated with tolerance and impaired glucose tolerance
1) Confidence 0.54 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.39 Pain Relevance 0.07
Prior studies in streptozotocin-treated mice using RNAi-directed downregulation of PEPCK-C in the liver have shown a direct role for this enzyme in the regulation of glucose homeostasis in the absence of insulin (12).
Negative_regulation (downregulation) of PEPCK in liver
2) Confidence 0.54 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.59 Pain Relevance 0
We have identified Sirt1 as a probable mediator in the response of the cell to a partial reduction in PEPCK-C content.
Spec (partial) Negative_regulation (reduction) of PEPCK
3) Confidence 0.47 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.46 Pain Relevance 0
These data suggest that insulin signaling through AKT-dependent FOXO1 phosphorylation contributes to the observed reduction in steady-state mRNA levels for gluconeogenic genes such as G6pc and Pck1.


Negative_regulation (reduction) of Pck1
4) Confidence 0.40 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.12 Pain Relevance 0
Finally, immunohistochemical analysis of PEPCK-C demonstrates a nonhomogeneous reduction of PEPCK-C immunoreactivity that is more evident in pericentral than periportal hepatocytes (Fig. 1B).


Negative_regulation (reduction) of PEPCK in hepatocytes
5) Confidence 0.40 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.19 Pain Relevance 0
Densitometric quantification of Western blots confirmed a similar amount of hepatic PEPCK-C protein reduction on treatment (100 ± 15.1 vs. 46.1 ± 6.8 relative units; n = 11, P < 0.01) (Fig. 1C and D).
Negative_regulation (reduction) of PEPCK
6) Confidence 0.40 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.17 Pain Relevance 0
Liver-specific knockout animals are euglycemic and able to bypass the complete absence of PEPCK-C activity in their livers with extrahepatic gluconeogenesis (8).
Negative_regulation (absence) of PEPCK in livers associated with targeted disruption
7) Confidence 0.40 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.18 Pain Relevance 0.04
In fact, 90% reduction in PEPCK-C protein levels in the liver, obtained with higher adenoviral dosage (Supplementary Fig. 1), reproduce the blockade on mitochondrial function observed in the knockout mice (36).
Negative_regulation (reduction) of PEPCK in liver associated with targeted disruption
8) Confidence 0.40 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.45 Pain Relevance 0
RESULTS—Treatment resulted in reduced PEPCK-C mRNA and protein.
Negative_regulation (reduced) of PEPCK
9) Confidence 0.39 Published 2008 Journal Diabetes Section Abstract Doc Link PMC2494684 Disease Relevance 0.42 Pain Relevance 0
Data presented in this manuscript, together with our previous study in streptozotocin-induced diabetic animals (12), demonstrate that a 50% reduction of PEPCK expression results in reduced HGO and glycemia.
Negative_regulation (reduction) of PEPCK associated with diabetes mellitus
10) Confidence 0.39 Published 2008 Journal Diabetes Section Body Doc Link PMC2494684 Disease Relevance 0.30 Pain Relevance 0
reduces hepatic glucose output along with downregulation of PEPCK and G6Pase expression (33).
Negative_regulation (downregulation) of PEPCK
11) Confidence 0.33 Published 2008 Journal Diabetes Section Body Doc Link PMC2494675 Disease Relevance 0.45 Pain Relevance 0.08
Specifically, increased LXR activity downregulates 11 beta-hydroxysteroid dehydrogenase type 1 (Stulnig et al 2002), downregules PPAR gamma, coactivator-1 alpha, and gluconeogenic enzymes such as PEPCK and glucose-6-phosphatase (Cao et al 2003; Laffitte et al 2003) and increases expression of glucokinase and GLUT-4 (Laffitte et al 2003).
Negative_regulation (downregules) of PEPCK
12) Confidence 0.08 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2291317 Disease Relevance 0.53 Pain Relevance 0.04
Another study suggests that FXR activation actually impairs hepatic gluconeogenic genes such as PEPCK (Ma et al 2006), and increases hepatic glycogen synthesis, all potentially mediated through enhanced insulin sensitivity.
Negative_regulation (impairs) of PEPCK
13) Confidence 0.08 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2291317 Disease Relevance 0.23 Pain Relevance 0.27

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