title: Human primary myoblast cell cultures from non-diabetic insulin resistant subjects retain defects in insulin action.
abstract: Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures. The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable in a uniform culture environment and is retained over time. The retention of insulin resistance in myoblast derived cell cultures is consistent with the expression of an underlying biochemical defect in insulin resistant skeletal muscle.
authors.affiliation: Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. bthompson@phx.niddk.nih.gov
authors.forename: D B
authors.initials: DB
authors.lastname: Thompson
authors.forename: R
authors.initials: R
authors.lastname: Pratley
authors.forename: V
authors.initials: V
authors.lastname: Ossowski
mesh_terms: D000185:Actinin / Q000276:immunology / Q000378:metabolism; D000328:Adult; D015152:Blotting, Northern; D003402:Creatine Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019085:Fluorescent Antibody Technique, Direct; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007198:Indians, North American; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics; D009218:Myosins / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators
chemical_list: D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; C497417:MYF5 protein, human; C503799:MYOG protein, human; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D015534:Trans-Activators; D000185:Actinin; D006003:Glycogen; D003402:Creatine Kinase; D009218:Myosins; D005947:Glucose