ArticleScientific reports2016
Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Rapamycin improves endometriosis‑related infertility involving ovarian senescence via the PPARα/IGFBP2 pathway.Molecular medicine reports · 2026Article
- Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes.International journal of molecular sciences · 2025Article
- Evaluating Fibroblast Growth Factor 21 (FGF21) Levels Post-Gastric Sleeve Surgery in Obese Patients.Cureus · 2024Article
- Mitigation of Diabetes Mellitus UsingJournal of diabetes research · 2024Article
- The metabolic effects of resumption of a high fat diet after weight loss are sex dependent in mice.Scientific reports · 2023Article
- The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial.Immunity & ageing : I & A · 2023Article
- Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis.Cell reports. Medicine · 2023Article
- Associations between insulin-like growth factor binding protein-2 and lipoprotein kinetics in men.Journal of lipid research · 2022Article
- Insulin-like growth factor role in determining the anti-cancer effect of metformin: RCT in prostate cancer patients.Endocrine connections · 2022Article
- Article
- IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.Cell reports. Medicine · 2021Article
- Inhibition of miR-199a-5p rejuvenates aged mesenchymal stem cells derived from patients with idiopathic pulmonary fibrosis and improves their therapeutic efficacy in experimental pulmonary fibrosis.Stem cell research & therapy · 2021Article
- Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder.Frontiers in psychiatry · 2021Article
- Metformin as a Potential Agent in the Treatment of Multiple Sclerosis.International journal of molecular sciences · 2020Review
- A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome.Scientific reports · 2020Article
- Effects of gastric sleeve surgery on the serum levels of GH, IGF-1 and IGF-binding protein 2 in healthy obese patients.BMC gastroenterology · 2020Article
- Ameliorative effects of black ginseng on nonalcoholic fatty liver disease in free fatty acid-induced HepG2 cells and high-fat/high-fructose diet-fed mice.Journal of ginseng research · 2020Article
- Resveratrol Attenuates High-Fat Diet Induced Hepatic Lipid Homeostasis Disorder and Decreases mFrontiers in pharmacology · 2020Article
- Leonurus japonicus Houtt Attenuates Nonalcoholic Fatty Liver Disease in Free Fatty Acid-Induced HepG2 Cells and Mice Fed a High-Fat Diet.Nutrients · 2017Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-diabetic drug, metformin, exerts its action through AMP-activated protein kinase (AMPK), and Sirtuin (Sirt1) signaling. Insulin-like growth factor (IGF)-binding protein 2 (IGFBP-2) prevents IGF-1 binding to its receptors, thereby contributing to modulate insulin sensitivity. In this study, we demonstrate that metformin upregulates Igfbp-2 expression through the AMPK-Sirt1-PPARα cascade pathway. In the liver of high fat diet, ob/ob, and db/db mice, Igfbp-2 expression was significantly decreased compared to the expression levels in the wild-type mice (p < 0.05). Upregulation of Igfbp-2 expression by metformin administration was disrupted by gene silencing of Ampk and Sirt1, and this phenomenon was not observed in Pparα-null mice. Notably, activation of IGF-1 receptor (IGF-1R)-dependent signaling by IGF-1 was inhibited by metformin. Finally, when compared to untreated type 2 diabetes patients, the metformin-treated diabetic patients showed increased IGFBP-2 levels with diminished serum IGF-1 levels. Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARα-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.