The biology of peroxisome proliferator-activated receptors: Relationship with lipid metabolism and insulin sensitivity

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms (alpha, delta, and gamma) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural acti...

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Vydáno v:	Diabetes (New York, N.Y.) Ročník 53; číslo 2; s. S43 - S50
Hlavní autor:	FERRE, Pascal
Médium:	Konferenční příspěvek Journal Article
Jazyk:	angličtina
Vydáno:	Alexandria, VA American Diabetes Association 01.02.2004
Témata:	Animals Associated diseases and complications Biological and medical sciences Care and treatment Case studies Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Fatty acids Health aspects Humans Hypoglycemic Agents - pharmacology Insulin - physiology Lipid Metabolism Medical sciences Organ Specificity Peroxisomes Receptors, Cytoplasmic and Nuclear - drug effects Receptors, Cytoplasmic and Nuclear - physiology Transcription Factors - drug effects Transcription Factors - physiology Type 2 diabetes France Endocrinopathy Pancreatic hormone Sensitivity Diabetes mellitus Lipids Metabolism Insulin Peroxisome proliferator activated receptor
ISSN:	0012-1797
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Shrnutí:	Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms (alpha, delta, and gamma) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural activating ligands are fatty acids and lipid-derived substrates. PPAR-alpha is present in liver, heart, and, to a lesser extent, skeletal muscle. When activated, it promotes fatty acid oxidation, ketone body synthesis, and glucose sparing. Fibrates, which are used as hypolipidemic drugs, are ligands of PPAR-alpha. PPAR-delta is ubiquitous and could also favor fatty acid oxidation in tissues in which PPAR-alpha is absent or less expressed. PPAR-gamma is expressed in adipose tissue, lower intestine, and cells involved in immunity. Activation of PPAR-gamma induces the differentiation of preadipocytes into adipocytes and stimulates triglyceride storage. Thiazolidinediones are compounds used as hypoglycemic, muscle insulin-sensitizing agents in type 2 diabetes. Unexpectedly, they are activators of PPAR-gamma. Their action on muscle insulin sensitivity may be secondary to the lowering of circulating lipids on PPAR-gamma activation and to the secretion by adipocytes of insulin-sensitizing hormones such as adiponectin, all promoting glucose utilization. The PPARs are thus major regulators of lipid and glucose metabolism, allowing adaptation to the prevailing nutritional environment.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	0012-1797
DOI:	10.2337/diabetes.53.2007.S43