The effect of PPARγ agonist on SGLT2 and glucagon expressions in alpha cells under hyperglycemia.
J Endocrinol Invest
; 40(10): 1069-1076, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28391584
ABSTRACT
BACKGROUND:
Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia.METHODS:
An Alpha TC1-6 cell line was cultured in control (5 mM) or hyperglycemia (HG, 15 mM) for 72 h. We applied troglitazone with or without PPARγ antagonist (GW9662 10 µM). To investigate the involvement of PI3K/Akt pathway, we applied troglitazone with or without Wortmanin. We measured sodium glucose transporter 2 (SGLT2) and glucagon (GCG) mRNA and protein expression. PPAR gamma, PI3K and Akt protein were also measured.RESULTS:
Exposure of alpha TC cells to HG for 72 h increased glucagon mRNA and protein expression. HG decreased SGLT2 mRNA and protein expression. Troglitazone significantly reversed HG-induced reduction of SGLT2 expression and increase of glucagon secretion. PPARγ antagonist (GW9662 10 µM) decreased the expression of SGLT2 and increased glucagon as HG did. Hyperglycemia increased PI3K and pAkt expression in alpha cells. Wortmanin (PI3K inhibitor, 1 µM) reversed HG-induced SGLT2 decrease and glucagon increase. Troglitazone treatment decreased PI3K and pAkt expression in HG.CONCLUSION:
In conclusion, PPARγ agonist, troglitazone improved glucose transport SGLT2 dysfunction and subsequent glucagon dysregulation in alpha cell under hyperglycemia. Those effects were through the involvement of PI3K/pAkt signaling pathway. This study may add one more reason for the ideal combination of PPARγ agonist and SGLT2 inhibitor in clinical practice.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glucagon
/
Regulação da Expressão Gênica
/
Cromanos
/
Tiazolidinedionas
/
PPAR gama
/
Células Secretoras de Glucagon
/
Transportador 2 de Glucose-Sódio
/
Hiperglicemia
Limite:
Animals
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Coréia do Sul