Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

INT-131, a novel, non-thiazolidinedione (TZD), selective peroxisome proliferator-activated receptor (PPAR)gamma modulator, is in development by InteKrin Therapeutics Inc for the treatment of type 2 diabetes mellitus (non-insulin dependent diabetes). The concept of selective modulation involves targeting and activating specific genes to minimize side effects while maintaining therapeutic benefits. In vitro, INT-131 attenuated adipogenic properties, indicating moderate PPARgamma activation/cofactor recruitment compared with the full agonistic properties of TZD compounds. INT-131 also compared favorably with TZDs in 6-month toxicity studies in rats and monkeys, exhibiting no increases in body or organ weights, and no relevant observations of edema or other fluid retention, which has been associated with congestive heart failure in TZDs. In phase I and II clinical trials, INT-131 was well tolerated, without any serious adverse events or reports of fluid retention. Antidiabetic efficacy was comparable with TZDs and was moderately greater than for other new, oral antidiabetic drugs, although only fasting plasma glucose levels were recorded. INT-131 appears to be a promising new PPARgamma agonist with potent antidiabetic actions and a favorable side effect profile; however, additional, extensive clinical investigation is required to justify the non-inferiority of this compound to TZDs and other oral antidiabetic drugs.
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PMID:INT-131, a PPARgamma agonist for the treatment of type 2 diabetes. 1933 60

The metabolic syndrome (MetS) is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, elevated blood pressure and combined dyslipidemia. In this review, we discuss the potential of farnesoid X receptor (FXR) agonists in the treatment of erectile dysfunction (ED), a multifactorial disorder often comorbid with MetS. FXR not only regulates lipid and glucose homeostasis but also influences endothelial function and atherosclerosis, suggesting a regulatory role for this hormone nuclear receptor in the cardiovascular complications associated with the MetS, including ED. MetS induces ED via several mechanisms, and in particular through endothelial dysfunction in penile vessels. In a high-fat diet rabbit model of MetS, a 3-month treatment with the potent and selective FXR agonist INT-747 restores endothelium-dependent relaxation in isolated cavernous tissue, normalizing responsiveness to acetylcholine and to electrical field stimulation. Accordingly, eNOS expression in the penis is greatly up-regulated by INT-747 treatment. Experiments in a rat model of chemically-induced type 1 diabetes further demonstrate that INT-747 treatment preserves erectile function induced by electrical stimulation of the cavernous nerve. These results add a new facet to the pleiotropic activities mediated by FXR, and reveal novel beneficial effects of FXR activation with potential clinical relevance. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
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PMID:Farnesoid X receptor activation improves erectile dysfunction in models of metabolic syndrome and diabetes. 2105 55