Effects of NIDDM on the glucose transport system in human skeletal muscle.
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.
Scheck
S H
SH
Department of Kinesiology, University of California, Los Angeles 90024-1527.
Barnard
R J
RJ
Lawani
L O
LO
Youngren
J F
JF
Martin
D A
DA
Singh
R
R
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
D001786:Blood Glucose; D007328:Insulin; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose