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

doi:10.1038/srep08145

Cited by 87 publications

(60 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The levels of urinary metabolites, including cortisol, hydroxycortisol (at boundary line statistically tolerance p=0.0575), betaine, and glucose decreased 12 h after metformin administration, while those of retinyl β-glucuronide and cholic acid glucuronide increased [22]. The studies by Henk den Ouden et al [23] and Irving et al [24] examining treatment with metformin alone for 5 years and in combination with pioglitazone for 3 months showed a decrease in the plasma glucose concentration.…”

Section: Literature Informationmentioning

confidence: 98%

“…The most common metabolites were those found in plasma analysis, except one article in which the metabolites were obtained in urinary analysis [22].…”

Section: Literature Informationmentioning

confidence: 99%

“…Moreover, the results of the study by Vinaixa et al showed that the serum levels of lysine, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol varied considerably; the levels of lysine and LDL cholesterol decreased by approximately 45.0% and 5.28%, respectively; however, the HDL cholesterol levels increased by 34.0%. Henk den Ouden et al [22] showed that after 5 years of follow up, metformin decreased the total plasma cholesterol. Samino et al [8] and Xu Tao et al [27] showed that the serum HDL cholesterol increased and LDL cholesterol decreased, respectively.…”

Section: Literature Informationmentioning

confidence: 99%

“…We identified many metabolites according to (1) various disease types (e.g., healthy [22] T2DM [9,[22][23][24][25] [26] (2) diverse number of patients (n=9 to 151); (3) different doses of metformin and its treatment period in the included trials (the shortest treatment period, 12 h and the longest follow-up period, 7 years); and (4) various analytical techniques used to identify metabolites from biological fluids (e.g., gas chromatography mass spectrometry [GC/MS], liquid chromatography mass spectrometry [LC/MS] and nuclear magnetic resonance [NMR]). We evaluated further details in the full-text article and included literature on the "metformin medication" regardless of above all conditions.…”

Section: Literature Informationmentioning

confidence: 99%

See 3 more Smart Citations

Mechanism by which Metformin Influence Metabolic Changes in Human: A Systematic-Review

Park¹,

Kim²,

Shin³

2016

J Diabetes Metab

View full text Add to dashboard Cite

Metformin is the most widely used oral antihyperglycemic agent for the improvement of type 2 diabetes mellitus (T2DM). In patients with T2DM, metformin increases insulin sensitivity and reduces glucose production. In this systematic review, we identified and compared metabolic changes induced by metformin administration.We searched articles published within the past 5 years on Pubmed.gov by using the keywords "metformin and metabolomics." No restrictions were placed on the languages, species, or gender during the selection of articles. From the 29 identified articles, we excluded non-human in vivo or in vitro studies, studies in cancer patients, and studies in which the focus was not on variation in the levels of metabolites after administration of medication such as pharmacogenetic studies. Finally, we selected 8 articles and compared their results.In the selected study results, a treatment with metformin and a combination of metformin and other anti-diabetic agents decreased the levels of phenylalanine, tyrosine, lysine, and glutamate to 5.58 ± 2.23%, 11.50 ± 2.12%, 25.28 ± 27.90%, and 35.49 ± 26.18% (mean ± SD), respectively, but increased the levels of alanine to 16.00% in 3 months-5 years of follow-up after metformin treatment compared to the control. The levels of total cholesterol and low-density lipoprotein (LDL) cholesterol (5.28%) decreased, whereas those of high-density lipoprotein (HDL) cholesterol increased by 34.65% in 18-30 months of follow-up after administration of metformin.Metformin administration in human alters the blood concentration of phenylalanine, tyrosine, glutamate and lysine. Further confirmatory studies are required to understand how these metabolites related to the drug mechanism and also drug response, and to develop the biomarkers for predicting metformin response in humans.

show abstract

Section: Literature Informationmentioning

confidence: 98%

“…The most common metabolites were those found in plasma analysis, except one article in which the metabolites were obtained in urinary analysis [22].…”

Section: Literature Informationmentioning

confidence: 99%

Section: Literature Informationmentioning

confidence: 99%

Section: Literature Informationmentioning

confidence: 99%

See 2 more Smart Citations

Mechanism by which Metformin Influence Metabolic Changes in Human: A Systematic-Review

Park¹,

Kim²,

Shin³

2016

J Diabetes Metab

View full text Add to dashboard Cite

show abstract

“…The device settings have been described in a previous study in detail [15]. The overall quality of the analysis procedure was monitored using repetition of a pooled serum or urine sample (data not shown).…”

Section: Untargeted Metabolite Profilingmentioning

confidence: 99%

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

Ban

Cho

Kim

et al. 2016

Clin Experimental Allergy

View full text Add to dashboard Cite

SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/QToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE 4 and LTE 4 /PGF 2 a ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE 4 and LTE 4 /PGF 2 a ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE 4 levels were significantly correlated with the fall in FEV 1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE 4 and LTE 4 /PGF 2 a ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/QToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

show abstract

Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus

Madsen

Chi

Metzendorf

et al. 2019

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether metformin can prevent or delay T2DM and its complications in people with increased risk of developing T2DM is unknown. OBJECTIVES: To assess the effects of metformin for the prevention or delay of T2DM and its associated complications in persons at increased risk for the T2DM. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was March 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of one year or more comparing metformin with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or standard care in people with impaired glucose tolerance, impaired fasting glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or combinations of these. DATA COLLECTION AND ANAL-YSIS: Two review authors read all abstracts and full-text articles and records, assessed risk of bias and extracted outcome data independently. We used a random-effects model to perform meta-analysis and calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 20 RCTs randomising 6774 participants. One trial contributed 48% of all participants. The duration of intervention in the trials varied from one to five years. We judged none of the trials to be at low risk of bias in all 'Risk of bias' domains. Our main outcome measures were all-cause mortality, incidence of T2DM, serious adverse events (SAEs), cardiovascular mortality, non-fatal myocardial infarction or stroke, health-related quality of life and socioeconomic effects.The following comparisons mostly reported only a fraction of our main outcome set. Fifteen RCTs compared metformin with diet and exercise with or without placebo: all-cause mortality was 7/1353 versus 7/1480 (RR 1.11, 95% CI 0.41 to 3.01; P = 0.83; 2833 participants, 5 trials; very low-quality evidence); incidence of T2DM was 324/1751 versus 529/1881 participants (RR 0.50, 95% CI 0.38 to 0.65; P < 0.001; 3632 participants, 12 trials; moderate-quality evidence); the reporting of SAEs was insufficient and diverse and meta-analysis could not be performed (reported numbers were 4/118 versus 2/191; 309 participants; 4 trials; very low-quality evidence); cardiovascular mortality was 1/1073 versus 4/1082 (2416 participants; 2 trials; very low-quality evidence). One trial reported no clear difference in health-related quality of life after 3.2 years ...

show abstract

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

Cited by 87 publications

References 30 publications

Mechanism by which Metformin Influence Metabolic Changes in Human: A Systematic-Review

Mechanism by which Metformin Influence Metabolic Changes in Human: A Systematic-Review

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus

Contact Info

Product

Resources

About