Biomaterial Database

Protein tyrosine phosphatase-1B in diabetes. 2000

B P Kennedy, and C Ramachandran

Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Pointe Claire-Dorval, H9R 4P8, Quebec, Canada. brian_kennedy@merck.com

A role for protein tyrosine phosphatases in the negative regulation of insulin signaling and a putative involvement in the insulin resistance associated with type 2 diabetes have been postulated since their discovery. The recent demonstration that mice lacking the protein tyrosine phosphatase-1B (PTP-1B) have enhanced insulin sensitivity validates this. Furthermore, when fed a high fat diet, these mice maintained insulin sensitivity and were resistant to obesity, suggesting that inhibition of PTP-1B activity could be a novel way of treating type 2 diabetes and obesity. This commentary reviews our current knowledge of PTP-1B in insulin signaling and its role in diabetes and discusses the development of potent and selective PTP-1B inhibitors.

UI	MeSH Term	Description	Entries
D007113	Immunity, Innate	The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.	Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D009765	Obesity	A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D003920	Diabetes Mellitus	A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D017027	Protein Tyrosine Phosphatases	An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.	Phosphotyrosine Phosphatase,Protein-Tyrosine-Phosphatase,Tyrosyl Phosphoprotein Phosphatase,PTPase,Phosphotyrosyl Protein Phosphatase,Protein-Tyrosine Phosphatase,Phosphatase, Phosphotyrosine,Phosphatase, Phosphotyrosyl Protein,Phosphatase, Protein-Tyrosine,Phosphatase, Tyrosyl Phosphoprotein,Phosphatases, Protein Tyrosine,Phosphoprotein Phosphatase, Tyrosyl,Protein Phosphatase, Phosphotyrosyl,Protein Tyrosine Phosphatase,Tyrosine Phosphatases, Protein
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054562	Protein Tyrosine Phosphatase, Non-Receptor Type 1	A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.	PTPase 1B,PTPase HA2,Protein Tyrosine Phosphatase 1B,Protein-Tyrosine Phosphatase HA2,Protein Tyrosine Phosphatase HA2,Protein Tyrosine Phosphatase, Non Receptor Type 1