Information about Thiazolidinedione
The medication class of thiazolidinedione (sometimes referred to as 'glitazones') was introduced in the late 1990s as an adjunctive therapy for diabetes mellitus (type 2) and related diseases.
Genes upregulated by PPARγ can be found in the main article on peroxisome proliferator-activated receptors.
By activating PPARγ:
Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:
It is being investigated experimentally in polycystic ovary syndrome (PCOS), non-alcoholic steatohepatitis (NASH),[2] psoriasis,[3] and other conditions.[4]
Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones. There are some indications that thiazolidinediones provide some degree of the protection against initial stages of the breast carcinoma development.
The main side effect of all thiazolidinediones is fluid retention, leading to edema, weight gain, and potentially aggravating heart failure. Therefore, thiazolidinediones should not be prescribed in patients with decreased ventricular function (NYHA grade III or IV heart failure).
Recent studies have shown there may be an increase risk of CHD with Rosiglitazone.[5] However, the PROactive study has shown that pioglitazone dose not have this same risk.
In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates
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Mode of action
Thiazolidinediones or TZDs act by binding to PPARs (peroxisome proliferator-activated receptors), a group of receptor molecules inside the cell nucleus, specifically PPARγ (gamma). The normal ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor migrates to the DNA, activating transcription of a number of specific genes.Genes upregulated by PPARγ can be found in the main article on peroxisome proliferator-activated receptors.
By activating PPARγ:
- Insulin resistance is decreased
- Adipocyte differentiation is modified
- VEGF-induced angiogenesis is inhibited[1]
- Leptin levels decrease (leading to an increased appetite)
- Levels of certain interleukins (e.g. IL-6) fall
- Adiponectin levels rise
Members of the class
)
Chemically, the members of this class are derivatives of the parent compound thiazolidinedione, and include:
- Rosiglitazone (Avandia)
- Pioglitazone (Actos)
- Troglitazone (Rezulin), which was withdrawn from the market due to an increased incidence of drug-induced hepatitis.
Uses
The only approved use of the thiazolidinediones is in diabetes mellitus type 2.It is being investigated experimentally in polycystic ovary syndrome (PCOS), non-alcoholic steatohepatitis (NASH),[2] psoriasis,[3] and other conditions.[4]
Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones. There are some indications that thiazolidinediones provide some degree of the protection against initial stages of the breast carcinoma development.
Side effects and contraindications
The withdrawal of troglitazone has led to concerns of other thiazolidinediones increasing the risk of hepatitis. Guidelines now mention that for the first year of thiazolidinedione therapy, a two- or three-monthly check of liver enzymes is conducted to ascertain that no liver damage is occurring.The main side effect of all thiazolidinediones is fluid retention, leading to edema, weight gain, and potentially aggravating heart failure. Therefore, thiazolidinediones should not be prescribed in patients with decreased ventricular function (NYHA grade III or IV heart failure).
Recent studies have shown there may be an increase risk of CHD with Rosiglitazone.[5] However, the PROactive study has shown that pioglitazone dose not have this same risk.
Footnotes
1. ^ Panigrahy D, Singer S, Shen LQ, et al (2002). "PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis". J. Clin. Invest. 110 (7): 923-32. PMID 12370270.
2. ^ Belfort R et. al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355(22): 2297-307. PMID 17135584 Clinical trial info
3. ^ Krentz AJ, Friedmann PS. Type 2 diabetes, psoriasis and thiazolidinediones. Int J Clin Pract 2006;60:362-3. PMID 16494655.
4. ^ Clinical Trials for Rosiglitazone - from ClinicalTrials.gov, a service of the U.S. National Institutes of Health
5. ^ Avandia to Carry Stronger Heart Failure Warning - Forbes.com. Retrieved on 2007-08-15.
2. ^ Belfort R et. al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355(22): 2297-307. PMID 17135584 Clinical trial info
3. ^ Krentz AJ, Friedmann PS. Type 2 diabetes, psoriasis and thiazolidinediones. Int J Clin Pract 2006;60:362-3. PMID 16494655.
4. ^ Clinical Trials for Rosiglitazone - from ClinicalTrials.gov, a service of the U.S. National Institutes of Health
5. ^ Avandia to Carry Stronger Heart Failure Warning - Forbes.com. Retrieved on 2007-08-15.
A medication, medicine or drug is any substance or combination of substances administered to human beings or animals to treat or prevent disease; alternatively to assist in medical diagnosis.
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Centuries: 19th century - 20th century - 21st century
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For the band, see .
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Diabetes mellitus
Classification & external resources
ICD-10 E 10. –E 14.
ICD-9 250
MedlinePlus 001214
eMedicine med/546 emerg/134
MeSH C18.452.394.
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Classification & external resources
ICD-10 E 10. –E 14.
ICD-9 250
MedlinePlus 001214
eMedicine med/546 emerg/134
MeSH C18.452.394.
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In cell biology, peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms that exist across biology. They are intimately connected to cellular metabolism (carbohydrate, lipid and protein) and cell differentiation.
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For other uses, see Receptor.
In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates
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nucleus (3) ribosome (4) vesicle (5) rough endoplasmic reticulum (ER) (6) Golgi apparatus (7) Cytoskeleton (8) smooth ER (9) mitochondria (10) vacuole (11) cytoplasm (12) lysosome (13) centrioles]]
In cell biology, the nucleus (pl.
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In cell biology, the nucleus (pl.
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In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as
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Types of Fats in Food
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- Unsaturated fat
- Monounsaturated fat
- Polyunsaturated fat
- Trans fat
- Omega: 3, 6, 9
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In biochemistry, eicosanoids are signaling molecules derived from omega-3 (ω-3) or omega-6 (ω-6) fats. They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system.
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Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. So to say, it is the transfer of genetic information from DNA into RNA.
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For a non-technical introduction to the topic, see .
A gene is a locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions...... Click the link for more information.
In cell biology, peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms that exist across biology. They are intimately connected to cellular metabolism (carbohydrate, lipid and protein) and cell differentiation.
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Insulin resistance
Classification & external resources
eMedicine med/1173
MeSH C18.452.394.968.500
Insulin resistance
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Classification & external resources
eMedicine med/1173
MeSH C18.452.394.968.500
Insulin resistance
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Adipocytes are the cells that primarily compose adipose tissue, specialized in storing energy as fat.
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Description
There are two types of adipose tissue, white adipose tissue (WAT) and brown adipose tissue (BAT), which are also known as white fat and brown fat,..... Click the link for more information.
Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel
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Identifiers
Symbol LEPR
Entrez 3953
HUGO 6554
OMIM 601007
RefSeq NM_002303
UniProt P48357
Other data
Locus Chr. 1 p31 Leptin
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Symbol LEPR
Entrez 3953
HUGO 6554
OMIM 601007
RefSeq NM_002303
UniProt P48357
Other data
Locus Chr. 1 p31 Leptin
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For the mineral, see .
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher lifeforms, and serves to regulate adequate energy intake to maintain metabolic needs...... Click the link for more information.
Interleukins are a group of cytokines (secreted signaling molecules) that were first seen to be expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The name is something of a relic though (the term was coined by Dr.
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Identifiers
Symbol ADIPOR1
Entrez 51094
HUGO 24040
OMIM 607945
RefSeq NM_015999
UniProt Q96A54
Other data
Locus Chr. 1 q32.1
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Symbol ADIPOR1
Entrez 51094
HUGO 24040
OMIM 607945
RefSeq NM_015999
UniProt Q96A54
Other data
Locus Chr. 1 q32.1
adiponectin receptor 2
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Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl).
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Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic (antihyperglycemic, antidiabetic) action. Pioglitazone is marketed as trademarks Actos in the USA and Glustin in Europe by the pharmaceutical company Takeda.
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Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones. It was introduced in the late 1990s but turned out to be associated with an idiosyncratic reaction leading to drug-induced hepatitis.
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Hepatitis
Classification & external resources
Alcoholic hepatitis evident by fatty change, cell necrosis, Mallory bodies
ICD-10 K 75.9
ICD-9 573.3
DiseasesDB 20061
MeSH D006505 Hepatitis (plural hepatitides
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Classification & external resources
Alcoholic hepatitis evident by fatty change, cell necrosis, Mallory bodies
ICD-10 K 75.9
ICD-9 573.3
DiseasesDB 20061
MeSH D006505 Hepatitis (plural hepatitides
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Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents.
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Diabetes mellitus
Classification & external resources
ICD-10 E 10. –E 14.
ICD-9 250
MedlinePlus 001214
eMedicine med/546 emerg/134
MeSH C18.452.394.
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Classification & external resources
ICD-10 E 10. –E 14.
ICD-9 250
MedlinePlus 001214
eMedicine med/546 emerg/134
MeSH C18.452.394.
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Polycystic ovary syndrome
Classification & external resources
Polycystic Ovary shown on ultrasound image
ICD-10 E 28.2
ICD-9 256.4
OMIM 184700
Polycystic Ovary Syndrome (also known clinically as Stein-Leventhal syndrome
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Classification & external resources
Polycystic Ovary shown on ultrasound image
ICD-10 E 28.2
ICD-9 256.4
OMIM 184700
Polycystic Ovary Syndrome (also known clinically as Stein-Leventhal syndrome
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Non-alcoholic steatohepatitis
Classification & external resources
ICD-10 K 76.0
ICD-9 571.8
DiseasesDB 29786
eMedicine med/775 Non-alcoholic fatty liver disease (NAFLD
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Classification & external resources
ICD-10 K 76.0
ICD-9 571.8
DiseasesDB 29786
eMedicine med/775 Non-alcoholic fatty liver disease (NAFLD
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MeSH D008060 Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. ("Lipo" is Latin for "fat" and "dystrophy" is Latin for "abnormal or degenerative condition".
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Breast cancer
Classification & external resources
Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.
ICD-10 C 50.
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Breast cancer
Classification & external resources
Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.
ICD-10 C 50.
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