4-Hydroxyisoleucine was demonstrated to stimulate glucose-dependent insulin secretion by a direct effect on pancreatic islets. In addition to stimulating insulin secretion, 4-hydroxyisoleucine reduced insulin resistance in muscle and/or liver by activating insulin receptor substrate-associated phosphoinositide 3 (PI3) kinase activity.
 |
Source | Mol Med Rep (2015). Figure 5. 4-Hydroxyisoleucine |
| Method | western blotting | |
| Cell Lines | IR HepG2 cells | |
| Concentrations | 5, 10, 20 and 40 μmol/l | |
| Incubation Time | 24 h | |
| Results | The results shown in Fig. 5B demonstrate that 4‑HIL dose‑dependently upregulated IRS‑1 and GLUT4 expression, downregulated the expression of p‑IRS‑1 and had no effect on IRS‑2 expression in IR HepG2 cells. |
 |
Source | Mol Med Rep (2015). Figure 4. 4-Hydroxyisoleucine |
| Method | western blotting | |
| Cell Lines | IR HepG2 cells | |
| Concentrations | 5, 10, 20 and 40 μmol/l | |
| Incubation Time | 24 h | |
| Results | Notably, 4‑HIL dose‑dependently downregulated and upregulated TACE and TIMP3 expression in IR HepG2 cells, respectively |
| Cell Experiment | |
|---|---|
| Cell lines | HepG2 cells |
| Preparation method | The established IR HepG2 cells were then treated with different concentrations of 4-HIL (0, 5, 10, 20 and 40 µmol/l) for 24 h and glucose uptake was determined as described above. |
| Concentrations | 0, 5, 10, 20 and 40 µmol/l |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Male Sprague-Dawley rats |
| Formulation | |
| Dosages | 10, 30, 100 mg/kg |
| Administration | p.o. |
| Molecular Weight | 147.17 |
| Formula | C6H13NO3 |
| CAS Number | 781658-23-9 |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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