Effect of insulin on GLUT-4 mRNA and protein concentrations in skeletal muscle of patients with NIDDM and their first-degree relatives.
We examined whether insulin resistance, i.e. impaired insulin stimulated glucose uptake in NIDDM patients and their first-degree relatives is associated with alterations in the effect of insulin on the expression of the GLUT-4 gene in skeletal muscle in vivo. Levels of GLUT-4 mRNA and protein were measured in muscle biopsies taken before and after a euglycaemic insulin clamp from 14 NIDDM patients, 13 of their first-degree relatives and 17 control subjects. Insulin stimulated glucose uptake was decreased in the diabetic subjects (19.8 +/- 3.0 mumol.kg LBM-1.min-1, both p < 0.001) compared with control subjects (44.1 +/- 2.5 mumol.kg LBM-1.min-1) and relatives (39.9 +/- 3.3 mumol.kg LBM-1.min-1). Basal GLUT-4 mRNA levels were significantly higher in diabetic subjects and relatives compared to control subjects (99 +/- 8 and 108 +/- 9 pg/micrograms RNA vs 68 +/- 5 pg/micrograms RNA; both p < 0.01). Insulin increased GLUT-4 mRNA levels in all control subjects (from 68 +/- 5 to 92 +/- 6 pg/micrograms RNA; p < 0.0001), but not in the diabetic patients (from 99 +/- 8 to 90 +/- 8 pg/micrograms RNA, NS), or their relatives (from 94 +/- 9 to 101 +/- 11 pg/micrograms RNA, NS). In the relatives, individual basal GLUT-4 mRNA concentrations varied between 55 and 137 pg/micrograms RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Schalin-Jäntti
C
C
Second Department of Medicine, Helsinki University, Finland.
Yki-Järvinen
H
H
Koranyi
L
L
Bourey
R
R
Lindström
J
J
Nikula-Ijäs
P
P
Franssila-Kallunki
A
A
Groop
L C
LC
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D005947:Glucose