Insulin resistance in type 2 (non-insulin-dependent) diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle.
To study whether insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus is due to a defect in the expression of the insulin-responsive glucose transporter gene (GLUT-4) in human skeletal muscle, we measured the level of GLUT-4 mRNA and (in some of the subjects) its protein in muscle biopsies taken from 14 insulin-resistant patients with Type 2 diabetes, 10 first-degree relatives of the diabetic patients and 12 insulin-sensitive control subjects. Insulin sensitivity was measured with a + 45 mU.m2(-1).min-1 euglycaemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. GLUT-4 mRNA was measured using a human GLUT-4 cDNA probe and GLUT-4 protein with a polyclonal antibody specific for the 15 amino acid carboxy-terminal peptide. Both Type 2 diabetic patients and their relatives showed impaired stimulation of total-body glucose disposal by insulin compared with control subjects (29.5 +/- 2.1 and 34.0 +/- 4.8 vs 57.9 +/- 3.1 mumol.kg lean body mass-1.min-1; p less than 0.01). This impairment in glucose disposal was primarily accounted for by a reduction in insulin-stimulated storage of glucose as glycogen (13.0 +/- 2.4 and 15.6 +/- 3.9 vs 36.9 +/- 2.2 mumol.kg lean body mass-1.min-1; p less than 0.01). The levels of GLUT-4 mRNA expressed both per microgram of total RNA and per microgram DNA, were higher in the diabetic patients compared with the control subjects (116 +/- 25 vs 53 +/- 10 pg/microgram RNA and 177 +/- 35 vs 112 +/- 29 pg/microgram DNA; p less than 0.05, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Eriksson
J
J
Fourth Department of Medicine, Helsinki University Hospital, Finland.
Koranyi
L
L
Bourey
R
R
Schalin-Jäntti
C
C
Widén
E
E
Mueckler
M
M
Permutt
A M
AM
Groop
L C
LC
D000328:Adult; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000032:analysis; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology*; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger