Increased activity of membrane glycoprotein PC-1 in the fibroblasts from non-insulin-dependent diabetes mellitus patients with insulin resistance.
Although most of patients with non-insulin-dependent diabetes mellitus (NIDDM) have insulin resistance, it is unknown whether a molecule might interfere with insulin action. Membrane glycoprotein PC-1 (plasma cell antigen-1), which inhibits insulin receptor tyrosine kinase activity, was isolated from fibroblasts of NIDDM patients. Because PC-1 content in skeletal muscle and adipose tissue correlated with whole body insulin sensitivity, PC-1 might play a role in insulin resistance. In order to know whether PC-1 activity of fibroblasts is also elevated in Japanese NIDDM patients, and whether PC-1 activity correlates with the parameters of insulin resistance in vivo or not, we measured PC-1 activity of cultured fibroblasts from 17 patients with NIDDM and seven healthy controls. PC-1 activity of the NIDDM patients was 85.2 +/- 33.1 nmol/mg per min (mean +/- S.D.), and was higher than that of healthy controls (42.6 +/- 12.7 nmol/mg per min, P = 0.0002). Insulin sensitivity was measured in 11 of 17 NIDDM patients by the artificial pancreas. PC-1 activity of the patients with insulin resistance (glucose infusion rate < 3.0 mg/kg per min, n = 7) was elevated to 99.9 +/- 31.9 nmol/mg per min, while that of the other patients (n = 4) was 55.3 +/- 7.5 nmol/mg per min (P = 0.003). In conclusion, glycoprotein PC-1 activity of dermal fibroblasts is correlated with insulin resistance in patients with NIDDM.
Teno
S
S
Diabetes Center, Tokyo Women's Medical University School of Medicine, Japan. teno@dmc.twmu.ac.jp
Kanno
H
H
Oga
S
S
Kumakura
S
S
Kanamuro
R
R
Iwamoto
Y
Y
D000328:Adult; D000368:Aged; D001706:Biopsy; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D012588:Scintillation Counting; D012867:Skin / Q000473:pathology
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008562:Membrane Glycoproteins; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1