ArticleDiabetologia2013
Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 14 citations in OpenAlex.
- Metagenomic and metabolomic analyses show correlations between intestinal microbiome diversity and microbiome metabolites in ob/ob and ApoEFrontiers in nutrition · 2022Article
- Small molecule IVQ, as a prodrug of gluconeogenesis inhibitor QVO, efficiently ameliorates glucose homeostasis in type 2 diabetic mice.Acta pharmacologica Sinica · 2019Article
- Gut Microbiota Composition and Structure of the Ob/Ob and Db/Db Mice.International journal of endocrinology · 2019Article
- Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.Frontiers in pharmacology · 2017Article
- Anti-diabetic activities of catalpol in db/db mice.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
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8 authors at 2 institutions in 1 country.
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Abstract
aims/hypothesisImprovement of glucose and lipid metabolic dysfunctions is a potent therapeutic strategy against type 2 diabetes mellitus, and identifying new functions for existing drugs may help accelerate the speed of new drug development. Here, we report that latanoprost, a clinical drug for treating primary open-angle glaucoma and intraocular hypertension, effectively ameliorated glucose and lipid disorders in two mouse models of type 2 diabetes. In addition, the glucose-lowering mechanisms of latanoprost were intensively investigated.
methodsA binding-affinity assay and enzymatic tests were used to determine the targets of latanoprost. Cell-based assays on 3T3-L1 adipocytes and C2C12 myotubes and animal model-based assays with db/db and ob/ob mice were further performed to clarify the mechanisms underlying latanoprost-regulated glucose and lipid metabolism.
resultsLatanoprost functioned as both an indirect activator of AMP-activated protein kinase and a selective retinoid X receptor α (RXRα) antagonist able to selectively antagonise the transcription of a RXRα/peroxisome proliferator-activated receptor γ heterodimer. It promoted glucose uptake, inhibited pre-adipocyte differentiation and regulated the main genes responsible for glucose and lipid metabolism, including Fas, Scd1, Perilipin (also known as Plin1), Lpl and Pdk4. Chronic administration of latanoprost in mice potently decreased the levels of fasting blood glucose, HbA1c, fructosamine (FMN), NEFA and total cholesterol, and effectively improved glucose tolerance and glucose/lipid metabolism-related genes in vivo. CONCLUSIONS/
interpretationOur studies demonstrate that the existing eye drug latanoprost is both an indirect activator of AMP-activated protein kinase and a selective RXRα antagonist. Latanoprost effectively ameliorated glucose and lipid disorders in diabetic mice, which strongly highlights the potential of latanoprost in the treatment of type 2 diabetes mellitus.
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