Adenosine A1 receptor is dispensable for hepatocyte glucose metabolism and insulin sensitivity.
Biochem Pharmacol
; 192: 114739, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34418353
ABSTRACT
Hepatic insulin resistance (IR) and enhanced hepatic glucose production (HGP) are key features of type 2 diabetes (T2D), contributing to fasting hyperglycemia. Adenosine receptors (ARs) are G protein-coupled and expressed in hepatocytes. Here, we explored the role of hepatic Gi/o-coupled A1AR on insulin resistance and glucose fluxes associated with obesity. We generated a mouse model with hepatocyte-specific deletion of A1AR (A1LΔ/Δ), which was compared with whole body knockout of A1AR or A1AR/A3AR (both Gi-coupled). Selective deletion of hepatic A1AR resulted in a modest improvement in insulin sensitivity. In addition, HFD A1LΔ/Δ mice showed decreased fasting glucose levels. Hyperinsulinemic-euglycemic clamp studies demonstrated enhanced insulin sensitivity with no change in HGP in HFD A1LΔ/Δ mice. Similar to A1LΔ/Δ, fasting blood glucose levels were significantly reduced in whole body A1Δ/Δ and A1Δ/ΔA3Δ/Δ compared to wild-type mice. Taken together, our data support the concept that blocking hepatic A1AR may decrease fasting blood glucose levels without directly affecting hepatocyte glucose metabolism and insulin sensitivity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Hepatócitos
/
Receptor A1 de Adenosina
/
Diabetes Mellitus Experimental
/
Glucose
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos