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Publication
Adenosine A1 receptor is dispensable for hepatocyte glucose metabolism and
insulin sensitivity.
Authors Jain S, Barella LF, Wess J, Reitman ML, Jacobson KA
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Biochemical pharmacology
Year 2021
Date Published 10/1/2021
Volume : Pages 192 : 114739
PubMed Reference 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 (A1L?/?), 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 A1L?/? mice showed decreased fasting glucose
levels. Hyperinsulinemic-euglycemic clamp studies demonstrated enhanced insulin
sensitivity with no change in HGP in HFD A1L?/? mice. Similar to A1L?/?, fasting
blood glucose levels were significantly reduced in whole body A1?/? and
A1?/?A3?/? 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.




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