Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus.
METHODS
Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM: The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined.


RESULTS
The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM: Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM:


CONCLUSIONS
NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM:
Kennington
A S
AS
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville.
Hill
C R
CR
Craig
J
J
Bogardus
C
C
Raz
I
I
Ortmeyer
H K
HK
Hansen
B C
BC
Romero
G
G
Larner
J
J
D000367:Age Factors; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D004285:Dogs; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism / Q000652:urine*; D007333:Insulin Resistance; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D012737:Sex Factors; D013329:Structure-Activity Relationship
D007294:Inositol