Insulin signaling, resistance, and metabolic syndrome: insights from mouse models into disease mechanisms
- Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A&M University Health Science Center, Scott & White, Central Texas Veterans Health Care System, 1901 South 1st Street, Bldg. 205, Temple, Texas 76504, USA
- Correspondence should be addressed to S Guo; Email: sguo{at}medicine.tamhsc.edu
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Figure 1
Insulin signaling cascade and interaction with intracellular signaling components from nutrients and cytokines involved in the control of cell metabolism, including the synthesis of glucose, glycogen, lipids and proteins, as well as other biological responses, such as autophagy, apoptosis, mitochondrial biogenesis, food intake, antioxidation, calcium handling, bone growth, and vascular dilation. PKA, protein kinase A; IR, insulin receptor; IRS, IR substrate; PI3K, phosphatidylinositol (PI)-3-kinase; PDK1, phosphoinositide-dependent protein kinase 1; CREB, cAMP response element-binding protein; CBP, CREB-binding protein; CRTC2, CREB-regulated cofactor 2; Foxo1, forkhead/winged helix transcription factor O class member 1; SREBP1, sterol response element-binding protein 1; Insig2, insulin induced gene 2; S6K, ribosome protein p70 S6 kinase; Gsk3, glycogen synthase kinase 3; GS, glycogen synthase; mTORC, mammalian target of rapamycin complex; TSC1/2, tuberous sclerosis complex 1/2; Rheb, Ras homolog enriched in brain; aPKC, atypical protein kinase C; AS160, Akt substrate 160 kDa protein; Bad, BCL2-associated agonist of cell death; PDK4, pyruvate dehydrogenase kinase 4; ACC, acetyl-CoA carboxylase; PEPCK, phosphoenolpyruvate carboxykinase; G6Pase, glucose-6-phosphatase; FAS, fatty acid synthase; MnSOD, manganese superoxide dismutase; TLR, Toll-like receptor; FFA, free fatty acids; ChREBP, carbohydrate-responsive element-binding protein; AMPK, AMP-dependent protein kinase; pY, phosphorylated tyrosine; TNFα, tumor necrosis factor α; pS/T, phosphorylated serine or threonine; Pomc, pro-opiomelanocortin; Agrp, Agouti-related peptide; Gpr 17, G-protein-coupled receptor 17; Serca2a (Atp2a2), sarco/endoplasmic reticulum Ca2+-ATPase; PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1α; Homx1, heme oxygenase 1; ATG8, autophagy-regulated gene 8; LC3 (MAP1L3A), microtubule-associated protein 1A/1B-light chain 3; eNOS, endothelial nitric oxide synthase; Glut, glucose transporter; JNK, c-Jun N-terminal kinase; IKKβ, inhibitor of NFκB kinase.
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Figure 2
Human Foxo1 phosphorylation, ubiquitination, methylation, acetylation, and glycosylation at amino acid residues via different pathways and enzymes. PRMT1, protein arginine methyltransferase 1; MST1, mammalian sterile 20-like kinase 1; CK, casein kinase; DYRK1A, dual-specific tyrosine-phosphorylated and -regulated kinase 1A; Ub, ubiquitin; SIRT2, NAD+-dependent histone deacetylase silent information regulator 2; CBP, CREB-binding protein; p300, global transcription factor cofactor; P, phosphorylation; Me, methylation; G, glycosylation; Ac, acetylation.
- © 2014 Society for Endocrinology
