GLUT4 degradation by GLUTFOURINH® in mice resembles moderate-obese diabetes of human with hyperglycemia and low lipid accumulation.
Biochim Biophys Acta Mol Basis Dis
; 1869(5): 166668, 2023 06.
Article
en En
| MEDLINE
| ID: mdl-36822448
ABSTRACT
BACKGROUNDS AND AIMS:
Type 2 diabetes mellitus (T2D) is a chronic disease characterized by insulin resistance and hyperglycemia. To investigate T2D, genetic and chemical induced hyper-obese rodent models have been experimentally developed. However, establishment of moderate-obese diabetes model will confer diverse opportunities for translational studies. In this study, we found the chemical, GLUTFOURINH® (GFI), induces post-translational degradation of glucose transporter 4 (GLUT4). We aimed to establish novel diabetic model by using GFI. METHODS ANDRESULTS:
Low plasma membrane GLUT4 (pmGLUT4) levels by GFI resulted in reduction of intracellular glucose uptake and TG, and increase of intracellular FFA in A204 cells. Likewise, GFI treatment decreased intracellular TG and increased intracellular FFA levels in Hep3B and 3T3-L1 cells. Mice were administered with GFI (16 mg/kg) for short-term (3-day) and long-term (28- and 31-day) to compared with vehicle injection, HFD model, and T2D model, respectively. Short-term and long-term GFI treatments induced hyperglycemia and hyperinsulinemia with low pmGLUT4 levels. Compared to HFD model, long-term GFI with HFD reduced adipose weight and intracellular TG accumulation, but increased plasma FFA. GFI treatment resulted in insulin resistance by showing low QUICKI and high HOMA-IR values, and low insulin response during insulin tolerance test. Additionally, low pmGLUT4 by GFI heightened hyperglycemia, hyperinsulinemia, and insulin resistance compared to T2D model.CONCLUSIONS:
In summary, we report GLUT4 degradation by novel chemical (GFI) induces moderate-obese diabetes representing hyperglycemia, insulin resistance and low intracellular lipid accumulation. The GLUT4 degradation by GFI has translational value for studying diseases related to moderate-obese diabetes.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
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Diabetes Mellitus Tipo 2
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Hiperglucemia
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Hiperinsulinismo
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2023
Tipo del documento:
Article