Adenosine A 1 receptor is dispensable for hepatocyte glucose metabolism and insulin sensitivity.

Autor: Jain S; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA., Barella LF; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA., Wess J; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA., Reitman ML; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA., Jacobson KA; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Electronic address: kennethj@niddk.nih.gov.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2021 Oct; Vol. 192, pp. 114739. Date of Electronic Publication: 2021 Aug 19.
DOI: 10.1016/j.bcp.2021.114739
Abstrakt: 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 G i/o -coupled A 1 AR on insulin resistance and glucose fluxes associated with obesity. We generated a mouse model with hepatocyte-specific deletion of A 1 AR (A1L Δ/Δ ), which was compared with whole body knockout of A 1 AR or A 1 AR/A 3 AR (both G i -coupled). Selective deletion of hepatic A 1 AR resulted in a modest improvement in insulin sensitivity. In addition, HFD A1L Δ/Δ mice showed decreased fasting glucose levels. Hyperinsulinemic-euglycemic clamp studies demonstrated enhanced insulin sensitivity with no change in HGP in HFD A1L Δ/Δ mice. Similar to A1L Δ/Δ , fasting blood glucose levels were significantly reduced in whole body A1 Δ/Δ and A1 Δ/Δ A3 Δ/Δ compared to wild-type mice. Taken together, our data support the concept that blocking hepatic A 1 AR may decrease fasting blood glucose levels without directly affecting hepatocyte glucose metabolism and insulin sensitivity.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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