Inositol phosphoglycans in diabetes and obesity: urinary levels of IPG A-type and IPG P-type, and relationship to pathophysiological changes.
Measurements have been made, in adult male diabetic patients and control subjects, of the urinary content of inositol phosphoglycans (IPGs), the IPG A-type and IPG P-type forms, which, among other actions, regulate pathways of glucose utilization, lipogenesis, triglyceride formation, and pyruvate dehydrogenase (PDH) activity. Urine samples from the entire diabetic group showed a 2- to 3-fold increase in IPG A-type, and a fall in the IPG P-type:IPG A-type ratio relative to the control group. Subdivision of the diabetic patients into lean IDDM and obese NIDDM groups revealed significant differences in the IPG P-type:IPG A-type ratio between these groups, this ratio decreasing with increases in the body mass index (BMI). Analysis of the relationships among IPGs and HbA1, blood pressure, and BMI indicated that a fall in the IPG P-type:IPG A-type ratio correlated with a rise in the HbA1 (indicative of impaired glycemic control), with increased systolic blood pressure and increased obesity, all factors linked to Syndrome X. There was a parallism between the profile of the IPG P-type:IPG A-type ratio and the well-established pattern of insulin resistance and BMI. In vitro studies of the effects of alterations in the IPG P-type:IPG A-type ratio on the activation of the pyruvate dehydrogenase complex (PDH complex) at the PDH phosphatase reaction demonstrated that IPG A-type forms antagonized the stimulation of the PDH phosphatase by IPG P-type forms, thus having a negative effect on the conversion of PDH to the active, dephosphorylated, form. This observation could provide a mechanism whereby the shifts in the IPG P-type:IPG A-type ratio reported above could change the metabolic pattern from one directed to glucose oxidation to one more directed toward energy conservation and lipid storage.
Kunjara
S
S
Department of Molecular Pathology, Molecular Medicine Unit, University College London Medical School, The Windeyer Building, 46, Cleveland Street, London, W1P 6DB, United Kingdom.
Wang
D Y
DY
Greenbaum
A L
AL
McLean
P
P
Kurtz
A
A
Rademacher
T W
TW
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D006442:Glycated Hemoglobin; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D007295:Inositol Phosphates / Q000652:urine*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000503:physiopathology / Q000652:urine*; D011134:Polysaccharides / Q000652:urine*; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism
D006442:Glycated Hemoglobin; D007295:Inositol Phosphates; D007328:Insulin; D011134:Polysaccharides; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; C028039:inositol phosphate glycan