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The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Antihyperglycemic mechanism of metformin occurs via the AMPK/LXRα/POMC pathway

Cho, Kumsun, Chung, Jae Yong, Cho, Sung Kweon, Shin, Hyun-Woo, Jang, In-Jin, Park, Jong-Wan, Yu, Kyung-Sang, Cho, Joo-Youn·2015·Scientific Reports
DOI 10.1038/srep08145PMC PMC4311245
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Abstract

Metformin is a first-line drug for treating type 2 diabetes. Although metformin is known to phosphorylate AMP-activated protein kinase (AMPK), it is unclear how the glucose-lowering effect of metformin is related to AMPK activation. The aim of this study was to identify the urinary endogenous metabolites affected by metformin and to identify the novel underlying molecular mechanisms related to its anti-diabetic effect. Fourteen healthy male subjects were orally administered metformin (1000 mg) once. First morning urine samples were taken before and after administration to obtain metabolomic data. We then further investigated the anti-diabetic mechanism of metformin in vitro and in vivo. The fluctuation of the metabolite cortisol indicated that the neuroendocrine system was involved in the anti-diabetic effect of metformin. Actually we found that metformin induced AMPK/liver X receptor α (LXRα) phosphorylation, followed by pro-opiomelanocortin (POMC) suppression in rat pituitary cells. We confirmed this result by administering metformin in an animal study. Given that cortisol stimulates gluconeogenesis, we propose the anti-hyperglycemic effect of metformin is attributed to reduced POMC/adrenocorticotropic hormone (ACTH)/cortisol levels following AMPK/LXRα phosphorylation in the pituitaries.

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Crossref · 10.1038/srep08145

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  • Metformin activates AMP-activated kinase (AMPK).

    “activation of AMP-activated kinase (AMPK) (Cho et al., 2015; Duca et al., 2015; Foretz et al., 2010; Lien et al., 2014; Lu et al., 2015; Zheng et al., 2012)”

    From Metformin as a tool to target aging (2016) · cites this paper as Cho et al., 2015

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Research works printed but not linked: 24

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  2. Abbasi, F. et al. Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53, 159–164 (2004). · DOI
  3. Phung, O. J., Scholle, J. M., Talwar, M. & Coleman, C. I. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain and hypoglycemia in type 2 diabetes. JAMA 303, 1410–1418 (2010). · DOI · Paper page
  4. Tahrani, A. A., Bailey, C. J., Del Prato, S. & Barnett, A. H. Management of type 2 diabetes: new and future developments in treatment. Lancet 378, 182–197 (2011). · DOI
  5. Tosca, L. et al. Metformin decreases GnRH- and activin-induced gonadotropin secretion in rat pituitary cells: potential involvement of adenosine 5' monophosphate-activated protein kinase (PRKA). Biol Reprod 84, 351–362 (2011). · DOI
  6. Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108, 1167–1174 (2001). · DOI · Paper page
  7. Labuzek, K. et al. Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol Rep 62, 956–965 (2010). · DOI
  8. Vermes, I., Steinmetz, E., Schoorl, J., van der Veen, E. A. & Tilders, F. J. Increased plasma levels of immunoreactive beta-endorphin and corticotropin in non-insulin-dependent diabetes. Lancet 2, 725–726 (1985). · DOI
  9. Matsumoto, S. et al. Liver X receptor-alpha regulates proopiomelanocortin (POMC) gene transcription in the pituitary. Mol Endocrinol 23, 47–60 (2009). · DOI
  10. Hwahng, S. H., Ki, S. H., Bae, E. J., Kim, H. E. & Kim, S. G. Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones. Hepatology 49, 1913–1925 (2009). · DOI
  11. Penniston, K. L. & Tanumihardjo, S. A. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 83, 191–201 (2006). · DOI
  12. Rolo, A. P., Oliveira, P. J., Moreno, A. J. & Palmeira, C. M. Bile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapy. Toxicol Sci. 57, 177–185 (2000). · DOI
  13. Woudenberg-Vrenken, T. E., Conde de la Rosa, L., Buist-Homan, M., Faber, K. N. & Moshage, H. Metformin protects rat hepatocytes against bile acid-induced apoptosis. PLoS One 8, e71773 (2013). · DOI
  14. SA, C. Betaine in human nutrition. Am J Clin Nutr 80, 539–549 (2004). · DOI · Paper page
  15. Iwasaki, Y. et al. Activation of AMP-activated protein kinase stimulates proopiomelanocortin gene transcription in AtT20 corticotroph cells. Am J Physiol Endocrinol Metab 292, E1899–1905 (2007). · DOI
  16. Guillod-Maximin, E. et al. Adiponectin receptors are expressed in hypothalamus and colocalized with proopiomelanocortin and neuropeptide Y in rodent arcuate neurons. J Endocrinol. 200, 93–105 (2009). · DOI
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  19. Han, S. M. et al. Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats. Diabetologia 48, 2170–2178 (2005). · DOI
  20. Claret, M. et al. AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 117, 2325–2336 (2007). · DOI
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Metadata

Authors
Cho, K., Chung, J. Y., Cho, S. K., Shin, H.-W., Jang, I.-J., Park, J.-W., Yu, K.-S., & Cho, J.-Y.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-01-30
Volume
5
Issue
1
ISSN
2045-2322
DOI
10.1038/srep08145
PMC
PMC4311245
Cited by
81
References
6
Language
en
Licence

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