title: Effects of NIDDM on the glucose transport system in human skeletal muscle.
abstract: The purpose of this study was to investigate cellular changes in the glucose transport system in skeletal muscle of lean non-insulin-dependent diabetes mellitus (NIDDM) compared to lean nondiabetic control patients. NIDDM patients had significantly elevated fasting levels (means +/- SE) of serum glucose (10.1 +/- 1.3 vs. 5.4 +/- 0.4 mM, P less than 0.001) and serum insulin (110.8 +/- 31.1 vs. 35.9 +/- 3.6 pM, P less than 0.0025). Basal glucose transport (35.1 +/- 5.5 vs. 30.8 +/- 8.0 pM/mg protein) and cytochalasin-beta binding (3.5 +/- 1.2 vs 3.8 +/- 1.0 pM/mg protein) in isolated sarcolemmal vesicles were not significantly different between NIDDM and control groups. Insulin binding was reduced in NIDDM (0.82 +/- 0.03 vs. 1.63 +/- 0.18 pM/mg protein) as was the Kd (0.93 +/- 0.03 vs. 1.38 + 0.12 nM). Tyrosine kinase activity, as assessed from incorporation of [32P]ATP into Glu 4:Tyr 1, was significantly (P less than 0.005) reduced in NIDDM at insulin concentrations from 1-100 nM. Maximum kinase activity was depressed (1.88 +/- 0.04 vs. 2.97 +/- 0.07 fM 32P/fM insulin binding at 100 nM insulin). The number of glucose transporters in the low-density microsomes was not significantly different between NIDDM and control groups (7.01 +/- 1.40 vs. 7.65 +/- 0.90 pM cytochalasin-beta bound/mg protein). These results suggest that decreased insulin binding and diminished receptor tyrosine kinase activity play a substantial role in the development of skeletal muscle insulin resistance associated with NIDDM.
authors.affiliation: Department of Kinesiology, University of California, Los Angeles 90024-1527.
authors.forename: S H
authors.initials: SH
authors.lastname: Scheck
authors.forename: R J
authors.initials: RJ
authors.lastname: Barnard
authors.forename: L O
authors.initials: LO
authors.lastname: Lawani
authors.forename: J F
authors.initials: JF
authors.lastname: Youngren
authors.forename: D A
authors.initials: DA
authors.lastname: Martin
authors.forename: R
authors.initials: R
authors.lastname: Singh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003571:Cytochalasin B / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D007328:Insulin; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose