title: Decreased insulin-stimulated 3-0-methylglucose transport in in vitro incubated muscle strips from type II diabetic subjects.
abstract: Peripheral insulin resistance in type II diabetes mellitus has been attributed to alterations in skeletal muscle glucose metabolism. However the direct dose-response relationship between insulin and glucose transport has not yet been studied in human skeletal muscle. We investigated 3-0-methylglucose transport in in vitro incubated skeletal muscle strips from eight healthy controls (age 61 +/- 6 yrs) and six lean type II diabetic patients treated with oral antidiabetic medication (age 73 +/- 3 yrs). Rectus abdominis muscle samples (approximately 1 g), obtained during elective abdominal surgery, were clamped at their resting length in vivo, whereupon strips (20-50 mg) were prepared for in vitro incubation. Measurements of high-energy phosphates and glycogen levels revealed that the muscle strips maintained energy levels during the incubation period. Glucose transport responded to insulin in a dose-response manner in the control group, with a 2-fold increase following maximal stimulation. Muscle strips from the diabetic group demonstrated a marked decrease in the insulin dose-response curve (P less than 0.01), when compared to healthy muscle strips. At a maximal insulin concentration (10,000 microU x ml-1), the response of the diabetic muscle tissue was 50% less than that of the healthy control tissue (P less than 0.05). This report demonstrates a dose-response curve for insulin stimulated 3-0-methylglucose transport in in vitro incubated human skeletal muscle strips. Furthermore, in type II diabetic muscle, our results provide evidence for one or several defects at a postreceptor level.
authors.affiliation: Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Andréasson
authors.forename: D
authors.initials: D
authors.lastname: Galuska
authors.forename: A
authors.initials: A
authors.lastname: Thörne
authors.forename: T
authors.initials: T
authors.lastname: Sonnenfeld
authors.forename: H
authors.initials: H
authors.lastname: Wallberg-Henriksson
mesh_terms: D019325:3-O-Methylglucose; D000368:Aged; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000493:pharmacokinetics*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism* / Q000503:physiopathology; D010710:Phosphates / Q000378:metabolism
chemical_list: D007328:Insulin; D008757:Methylglucosides; D010710:Phosphates; D019325:3-O-Methylglucose; D006003:Glycogen