Inhibition of AMP Deaminase Activity Does Not Improve Glucose Control in Rodent Models of Insulin Resistance or Diabetes
作者： Therese Admyre , Lena Amrot-Fors , Maria Andersson , Martin Bauer , Mikael Bjursell
DOI: 10.1016/J.CHEMBIOL.2014.09.011
关键词:
摘要: Inhibition of AMP deaminase (AMPD) holds the potential to elevate intracellular adenosine and levels and, therefore, augment signaling activation AMP-activated protein kinase (AMPK). To test latter hypothesis, novel AMPD pan inhibitors were synthesized explored using a panel in vitro, ex vivo, vivo models focusing on confirming inhibitory potency inhibition improve glucose control vivo. Repeated dosing selected did not insulin-resistant or diabetic rodent disease models. Mice with genetic deletion muscle-specific isoform Ampd1 showany favorable metabolic phenotype despite being challenged high-fat diet feeding. Therefore, these results do support development for treatment type 2 diabetes.
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