Open AccessAdropin reduces blood glucose levels in mice by limiting hepatic glucose production
Author(s) -
Thapa Dharendra,
Xie Bingxian,
Manning Janet R.,
Zhang Manling,
Stoner Michael W.,
Huckestein Brydie R.,
Edmunds Lia R.,
Zhang Xueyang,
Dedousis Nikolaos L.,
O'Doherty Robert M.,
Jurczak Michael J.,
Scott Iain
Publication year - 2019
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14043
Subject(s) - medicine , endocrinology , carbohydrate metabolism , insulin resistance , glucose uptake , metabolism , in vivo , insulin , skeletal muscle , biology , chemistry , microbiology and biotechnology
Adropin is a liver‐ and brain‐secreted peptide hormone with striking effects on fuel metabolism regulation in a number of tissues. Previous studies demonstrated that adropin secretion is decreased in obese mice subjected to a long‐term high‐fat diet ( HFD ), and that whole‐body loss of adropin expression resulted in systemic insulin resistance. Treatment of obese mice with adropin improves glucose tolerance, which has been linked to increased glucose oxidation and inhibition of fatty acid utilization in isolated skeletal muscle homogenates. In this study, we used in vivo physiological measurements to determine how treatment of obese mice with adropin affects whole‐body glucose metabolism. Treatment with adropin reduced fasting blood glucose and, as shown previously, increased glucose tolerance in HFD mice during standard glucose tolerance tests. Under hyperinsulinemic‐euglycemic clamp conditions, adropin treatment led to a nonsignificant increase in whole‐body insulin sensitivity, and a significant reduction in whole‐body glucose uptake. Finally, we show that adropin treatment suppressed hepatic glucose production and improved hepatic insulin sensitivity. This correlated with reduced expression of fatty acid import proteins and gluconeogenic regulatory enzymes in the liver, suggesting that adropin treatment may impact the pathways that drive vital aspects of hepatic glucose metabolism.