PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. 1998

B M Spiegelman
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. bruce_spiegelman@dfci.harvard.edu

The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functional receptor for the thiazolidinedione class of insulin-sensitizing drugs. This review examines the evidence that has implicated this transcription factor in the processes of adipogenesis and systemic insulin action. In addition, several models are discussed that may explain how a single protein can be involved in these related but distinct physiological actions. I also point out several important areas where our knowledge is incomplete and more research is needed. Finally, I discuss how advances in our understanding of nuclear receptor function, particularly the docking of cofactors in a ligand-dependent fashion, should lead to improved drugs that utilize the PPAR-gamma system for the treatment of insulin resistance.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003924 Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,MODY,Maturity-Onset Diabetes Mellitus,NIDDM,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Noninsulin Dependent,Diabetes Mellitus, Noninsulin-Dependent,Diabetes Mellitus, Type II,Maturity-Onset Diabetes,Noninsulin-Dependent Diabetes Mellitus,Type 2 Diabetes,Type 2 Diabetes Mellitus,Adult-Onset Diabetes Mellitus,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Slow Onset,Diabetes, Maturity-Onset,Diabetes, Type 2,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes,Maturity Onset Diabetes Mellitus,Non-Insulin-Dependent Diabetes Mellitus,Noninsulin Dependent Diabetes Mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000273 Adipose Tissue Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white. Fatty Tissue,Body Fat,Fat Pad,Fat Pads,Pad, Fat,Pads, Fat,Tissue, Adipose,Tissue, Fatty
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole

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