Circulating factors and insulin resistance. I. A novel myoinositol 1,2-cyclic phosphate phosphoglycan insulin antagonist from human plasma is elevated in noninsulin-dependent diabetes mellitus.
A novel low mol wt inositol phosphoglycan inhibitor (M tau 1200-1500) of insulin action in rat adipocytes has been partially purified from normal human plasma. This inhibitor, termed fraction V after the first purification step and fraction V3 after the second, is different from other reported serum insulin antagonists. It contains myoinositol, galactosamine, and mannose in approximate molar ratios of 1:1:3.3. The myoinositol has a 1,2-cyclic phosphate substituent, which is essential for the inhibitory activity. Its inhibitory activity is significantly elevated (161%, P < 0.05 for fraction V; 278%, P < 0.05 for fraction V3) in plasma of humans with noninsulin-dependent diabetes mellitus as compared with plasma of nondiabetic controls. These findings represent the first report of a naturally occurring mammalian inositol 1,2-cyclic phosphate containing phosphoglycan related to insulin action.
Galasko
G T
GT
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Bao
Y
Y
Broomfield
S J
SJ
Hooper
N M
NM
Turner
A J
AJ
Larner
J
J
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000818:Animals; D002850:Chromatography, Gel; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007294:Inositol / Q000032:analysis; D007295:Inositol Phosphates / Q000032:analysis* / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009005:Monosaccharides / Q000032:analysis; D011134:Polysaccharides / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D012016:Reference Values
D007295:Inositol Phosphates; D007328:Insulin; D007329:Insulin Antagonists; D008055:Lipids; D009005:Monosaccharides; D011134:Polysaccharides; C028039:inositol phosphate glycan; C010199:inositol cyclic phosphate; D007294:Inositol