Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand for RXR, active in concentrations near its physiological levels. It is thus reasonable to suspect that phytanic acid may have utility for treatment and prevention of human type 2 diabetes. Phytanic acid may mimic or complement various effects of conjugated linoleic acids, which have been shown to activate PPAR-gamma/RXR and prevent rodent diabetes. Administration of hydrolyzed chlorophyll may represent the most cost-effective strategy for raising human tissue levels of phytanic acid.
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PMID:The chlorophyll metabolite phytanic acid is a natural rexinoid--potential for treatment and prevention of diabetes. 1142 90

Phytanic acid, a metabolite of the chlorophyll molecule, is part of the human diet and is present in normal human serum at low micromolar concentrations. It was previously shown to be a ligand of the 9-cis-retinoic acid receptor and peroxisome proliferator-activated receptor (PPAR) a. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARa, but it also acts via PPARb and PPARg in CV-1 cells that have been cotransfected with the respective full-length receptor and an acyl-CoA oxidase-PPAR-responsive element-luciferase construct. We observed that, in contrast to other fatty acids, phytanic acid at physiological concentrations enhances uptake of 2-deoxy-D-glucose in rat primary hepatocytes. This result could be explained by the increase in mRNA expression of glucose transporters-1 and -2 and glucokinase, as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Compared with the PPARg-specific agonist ciglitazone, phytanic acid exerts only minor effects on the differentiation of C3H10T1/2 cells into mature adipocytes. These results clearly demonstrate that phytanic acid acts via different PPAR isoforms to modulate expression of genes involved in glucose metabolism, thus suggesting a potential role of phytanic acid in the management of insulin resistance.
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PMID:Phytanic acid, a natural peroxisome proliferator-activated receptor (PPAR) agonist, regulates glucose metabolism in rat primary hepatocytes. 1192 21

Phytanic acid is a derivative of the phytol side-chain of chlorophyll. It appears in humans following the ingestion of fat-containing foods and is present in human blood at a low micromolar concentration. It may activate retinoid X receptors (RXR) or peroxisome proliferator-activated receptor (PPAR) alpha in vitro. Phytanic acid induced the adipocyte differentiation of 3T3-L1 cells in culture as assessed by accumulation of lipid droplets and induction of the aP2 mRNA marker. This effect was mimicked by a synthetic activator of RXR but not by a PPARalpha agonist or by palmitic acid. In human pre-adipocytes in primary culture, phytanic acid also induced adipocyte differentiation. These findings indicate that phytanic acid may act as a natural rexinoid in adipose cells and suggest a potential use in the treatment of human type 2 diabetes and obesity.
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PMID:The chlorophyll-derived metabolite phytanic acid induces white adipocyte differentiation. 1218 8

Phytanic acid is a methyl-branched fatty acid present in the human diet, derived from the enzymatic degradation of phytol and subsequently oxidized by the rumenal microbiota and certain marine organisms. Consequently, phytanic acid is carried into the human body by means of food ingestion, mostly via red meat, dairy products and fatty marine foods. This fatty acid accumulates in people with some peroxisomal disorders and is traditionally related to neurological damage. However, some benefits derived from phytanic acid intake have also been described, such as the prevention of metabolic syndrome or type 2 diabetes. The aim of this work was to conduct an overview of the literature on the phytanic acid content of foods, management of the phytanic content during food production and biochemical mechanisms of phytanic acid metabolism, as well as to assess the evidence for the health benefits and risks of phytanic acid consumption in human health.
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PMID:Phytanic acid consumption and human health, risks, benefits and future trends: A review. 2797 98