Insulin Resistance Pathway

Preferred Label : Insulin Resistance Pathway;

NCIt related terms : Reversal of Insulin Resistance by Leptin;

Alternative definition : BIOCARTA: The insulin resistance of type II diabetes appears to be caused in part by the presence of high levels of lipids in cells such as skeletal muscle where this would not normally be found. The presence of excess lipid stores in skeletal muscle cells interferes with energy metabolism, impairing glucose oxidation and insulin response. Skeletal muscle is one of the primary glucose-consuming tissues, giving it a central role in insulin resistance. The increased risk of diabetes associated with obesity may be caused by increased lipid deposits in skeletal muscle and liver, creating insulin resistance. Leptin is a peptide hormone secreted by adipose tissue that has been associated with many processes. One of the target tissues of leptin is the hypothalamus where it can act to regulate feeding behavior and metabolism. Another leptin target is skeletal muscle. Activation of leptin signaling in skeletal muscle activates the AMP-activated protein kinase (AMP-kinase), known to play a key role in signaling in response to nutrients throughout evolution. AMPK phosphorylates and inactivates the enzyme ACC, acetyl-CoA carboxylase. ACC catalyzes the production of malonyl-CoA from acetyl-CoA. Malonyl-CoA in turn is an inhibitor of the import of fatty acids into mitochondria by carnitine palmitoyltransferase I for oxidation and energy production. In the presence of leptin, AMPK is activated, ACC is inhibited, and malonyl-CoA levels fall, increasing the oxidation of fatty acids and reducing the lipid content of cells. The reduced lipid content in skeletal muscle allows insulin signaling and glucose consumption to return to their normal levels, reducing insulin resistance. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_leptinPathway;

Details

Origin ID

C39139;

UMLS CUI

C1512803;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- 5'-AMP-Activated Protein Kinase [NCIt concept]
- 5'-AMP-Activated Protein Kinase Catalytic Subunit Alpha-1 [NCIt concept]
- 5'-AMP-Activated Protein Kinase Catalytic Subunit Alpha-2 [NCIt concept]
- Acetyl-CoA Carboxylase 1 [NCIt concept]
- Glucose-6-Phosphatase 3 [NCIt concept]
- Leptin [NCIt concept]
- Leptin Receptor [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Oxysterols Receptor LXR-Alpha [NCIt concept]
- Platelet Glycoprotein 4 [NCIt concept]
- Serine/Threonine-Protein Phosphatase 2A Activator [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1A [NCIt concept]
pathway_has_gene_element
- ACACA wt Allele [NCIt concept]
- CD36 wt Allele [NCIt concept]
- G6PC3 wt Allele [NCIt concept]
- LEP wt Allele [NCIt concept]
- LEPR wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- NR1H3 wt Allele [NCIt concept]
- PRKAA1 wt Allele [NCIt concept]
- PRKAA2 wt Allele [NCIt concept]
- PTPA wt Allele [NCIt concept]
- TNFRSF1A wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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