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| In vitro insulin resistance model | Inducing methods | Important findings | References |
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| C2C12 myotube and HepG2 | 0.25 mM palmitic acid solution in a serum-free medium with 1% FFA-free bovine serum albumin (BSA) for 24 hours of incubation | (i) The glucose uptake and p-Akt declined significantly on both cell lines
(ii) The decrease in expression of GLUT2 and GLUT4 on HepG2 and C2C12 myotubes, respectively
(iii) The increasing glucose content in both cell lines | [33] |
|
| C2C12 myotube | 0.75 mM palmitic acid in 10% FFA-free BSA-DMEM for 16 hours of incubation | (i) The significantly reduced 2-NBDG uptake in insulin-stimulated C2C12 myotubes
(ii) The inhibition of GLUT4 translocation
(iii) Downregulation of Tyr632 phosphorylation of insulin receptor substrate 1 (IRS-1) while upregulation IRS-1 Ser307 phosphorylation | [35] |
|
| C2C12 myotube | 0.75–1 mM palmitic acid in DMEM containing 2% (w/v) FFA-free BSA and 2% calf serum for 16 hours of incubation | (i) Palmitate (C16: 0) inhibits GLUT4 trafficking by inducing sortilin downregulation via a PKC-θ-mediated mechanism
(ii) It also significantly promotes the TNF-α secretion | [36] |
|
| C2C12 myotube | 750 μM palmitate in DMEM containing 2% FFA-free bovine serum albumin | (i) The increase of PKC-θ and ERK phosphorylation
(ii) The reduction of 2-deoxy glucose uptake, p-Akt, and GLUT4 translocation | [39] |
|
| C2C12 myotube | 0.75 mM palmitic acid in DMEM containing 1% FFA-free BSA for 16 hours of incubation | (i) The upregulation of TNF-α protein expression
(ii) The suppression of insulin-stimulated phosphorylation of IRS-1 and Akt at Tyr632 and Ser473, respectively
(iii) The inhibition of insulin-dependent glucose uptake | [40] |
|
| C2C12 myotube | 0.25 mM palmitate solution in FFA-free BSA for 20 hours of incubation | (i) Stimulation of both IL-6 mRNA expression and protein secretion by a proteasome-dependent pathway which results in rapid and chronic activation of nuclear factor-κB | [42] |
|
| HepG2 | 750 μM palmitate coupled to BSA for 18 hours of incubation | (i) Lowered insulin-stimulated Akt phosphorylation and glycogen synthesis, along with increased glucose-6-phosphatase expression
(ii) This process is related to endoplasmic reticulum (ER) stress induction | [44] |
|
| HepG2 | A high concentration of glucose (55 mM) for 24 hours | (i) Triggers glucose production while suppressing glucose uptake with mechanisms related to AKT inhibition and the upregulation of PEPCK and G6Pase expression | [48] |
|
| HepG2 | High concentration of glucose (30 mM) in serum-free DMEM for 24 hours | (i) A significant inhibition of Akt phosphorylation | [49] |
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| Fully differentiated 3T3-L1 | High glucose at a concentration 25 mM and 0.6 nM insulin for 18 hours of incubation | (i) The inhibition of 2-deoxy-[3H]-d-glucose uptake and an increase in TNF-α | [50] |
|
| Fully differentiated 3T3-L1 | Human recombinant insulin (150 nM), which was added from day 6 of postdifferentiation induction until the day before the experiments | (i) Impairment of insulin signaling (lower p-Akt, p-IRS1, and p-IR) | [14] |
|
| C2C12 myotube | Chronic insulin concentrations of 60 nM for 24 hours | (i) The inhibition of insulin signaling, especially p-Akt | [5] |
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| C2C12 myotube | Chronic insulin exposure (100 nM) for 3 days | (i) Lowered 2-deoxy glucose uptake
(ii) The inhibition of AMPK pathway | [52] |
|
| Fully differentiated 3T3-L1 | 24 hours of insulin incubation at a concentration of 10−6 mol/L | (i) The downregulation of the glucose uptake-related pathways (GLUT4, Akt, and p-Akt)
(ii) Inhibition of insulin-sensitive signaling pathways, including IRS1, PPARγ, PI3K, and p38-MAPK, at both mRNA and protein levels | [53] |
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