The Liver Circadian Clock Modulates Biochemical and Physiological Responses to Metformin
(2017) In Journal of Biological Rhythms 32(4). p.345-358- Abstract
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice. Furthermore, we demonstrate that while metformin transport into hepatocytes is unaltered by time of day, the kinetics of... (More)
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice. Furthermore, we demonstrate that while metformin transport into hepatocytes is unaltered by time of day, the kinetics of metformin-induced activation of AMP-activated protein kinase (AMPK) in the liver are remarkably altered with circadian time. Liver-specific ablation of Bmal1 expression alters metformin induction of AMPK and blood glucose response but does not completely abolish time of day differences. Together, these data demonstrate that circadian rhythms affect the biological responses to metformin in a complex manner.
(Less)
- author
- organization
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- AMPK, circadian, diabetes, liver, metformin
- in
- Journal of Biological Rhythms
- volume
- 32
- issue
- 4
- pages
- 14 pages
- publisher
- SAGE Publications
- external identifiers
-
- pmid:28816632
- wos:000408277100006
- scopus:85027679704
- ISSN
- 0748-7304
- DOI
- 10.1177/0748730417710348
- language
- English
- LU publication?
- no
- id
- 3b9deb59-87fb-4728-8159-2f61c2fb0c5b
- date added to LUP
- 2017-09-04 09:33:25
- date last changed
- 2024-01-14 04:17:41
@article{3b9deb59-87fb-4728-8159-2f61c2fb0c5b,
abstract = {{<p>Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice. Furthermore, we demonstrate that while metformin transport into hepatocytes is unaltered by time of day, the kinetics of metformin-induced activation of AMP-activated protein kinase (AMPK) in the liver are remarkably altered with circadian time. Liver-specific ablation of Bmal1 expression alters metformin induction of AMPK and blood glucose response but does not completely abolish time of day differences. Together, these data demonstrate that circadian rhythms affect the biological responses to metformin in a complex manner.</p>}},
author = {{Henriksson, Emma and Huber, Anne Laure and Soto, Erin K. and Kriebs, Anna and Vaughan, Megan E. and Duglan, Drew and Chan, Alanna B. and Papp, Stephanie J. and Nguyen, Madelena and Afetian, Megan E. and Lamia, Katja A}},
issn = {{0748-7304}},
keywords = {{AMPK; circadian; diabetes; liver; metformin}},
language = {{eng}},
number = {{4}},
pages = {{345--358}},
publisher = {{SAGE Publications}},
series = {{Journal of Biological Rhythms}},
title = {{The Liver Circadian Clock Modulates Biochemical and Physiological Responses to Metformin}},
url = {{http://dx.doi.org/10.1177/0748730417710348}},
doi = {{10.1177/0748730417710348}},
volume = {{32}},
year = {{2017}},
}