Biomaterial Database

Insulin stimulation of mitogen-activated protein kinase, p90rsk, and p70 S6 kinase in skeletal muscle of normal and insulin-resistant mice. Implications for the regulation of glycogen synthase. 1995

P Y Chang, and Y Le Marchand-Brustel, and L A Cheatham, and D E Moller

Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.

Skeletal muscles from mice stimulated with insulin in vivo were used to evaluate relationships between the insulin receptor tyrosine kinase, mitogen-activated protein (MAP) kinase, p90rsk, p70 S6 kinase (p70S6k), and glycogen synthase. Two models of insulin resistance were also evaluated: (a) transgenic mice with a severe insulin receptor defect and (b) gold thioglucose (GTG) mice (obesity with minimal insulin receptor dysfunction). In normal mice, insulin stimulated MAP kinase (6-fold), p90rsk (RSK2, 5-fold), p70S6k (10-fold), and glycogen synthase (30-50% increase in fractional velocity). In transgenic mice, stimulation of MAP kinase and RSK2 were not detectable, whereas activation of p70S6k and glycogen synthase were preserved. In GTG mice, activation of MAP kinase, RSK2, p70S6k, and glycogen synthase were impaired. Since p70S6k and glycogen synthase were correlated, rapamycin was used to block p70S6k, and glycogen synthase activation was unaffected in normal mice; however, it was partially impaired in transgenic mice. CONCLUSIONS (a) stimulation of p70S6k and glycogen synthase are selectively preserved in muscles with a severe insulin receptor kinase defect, indicating signal amplification in pathways leading to these effects; (b) MAP kinase-RSK2 and p70S6k activation are impaired in obese mice, suggesting multiple loci for postreceptor insulin resistance; (c) glycogen synthase was dissociated from MAP kinase and RSK2, indicating that they are not required for this effect of insulin; and (d) p70S6k is not essential for glycogen synthase activation, but it may participate in redundant signaling pathways leading to this effect of insulin.

UI	MeSH Term	Description	Entries
D007166	Immunosuppressive Agents	Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.	Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
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
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
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).
D011090	Polyenes	Hydrocarbons with more than one double bond. They are a reduced form of POLYYNES.	Cumulenes
D011494	Protein Kinases	A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.	Protein Kinase,Kinase, Protein,Kinases, Protein
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
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference