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Reagents for the Measurement of Myoinositol (MI) Lucica MI

Myoinositol (MI) Q&A

Q1:
What kind of substance is myoinositol?
Myoinositol is an inositol, which is a cyclic isomer of D-glucose. This very stable substance displays a structure similar to D-glucose. Inositol exists as 9 stereoisomers, but myoinositol accounts for 95% of inositol in the body.1 In humans, myoinositol is supplied in a total amount of about 3 g/day, including 1 g from food and 2 g by biosynthesis from glucose-6-phosphate.2

Myoinositol

D-glucose

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Q2:
Where is myoinositol in the body and what role does it play?
Myoinositol is mainly present in cells (at concentrations several tenfold higher than in blood) and exists widely in vivo as the free form or as phosphatidylinositol components.2,3 Phosphatidylinositol is degraded by activation of certain receptors for inositol-3-phosphate, which functions as an intracellular "second messenger".4 In diabetic states (hyperglycemia), particularly in the nervous system, intracellular myoinositol decreases (sorbitol increases), ultimately leading to reduced Na, K-ATPase activity and impaired neural transmission. 2, 5
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Q3:
What is the significance of measuring myoinositol?
Measurement of urinary myoinositol after glucose loading can detect impaired glucose tolerance (IGT). In 1858, high concentrations of myoinositol were discovered in the urine of diabetic patients (10 times higher in diabetic patients).6 This suggests the usefulness of urinary myoinositol as an index of glucose intolerance. In addition, Kawazu et al. reported that ΔUMI before and after a 75-g OGTT correlates well with glucose levels after glucose loading, and that ΔUMI after a glucose load is a good indicator of hyperglycemic state that may be undetected during fasting.7 Correlations between myoinositol and both diabetic neuropathy and nephropathy have also received attention.8
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Q4:
Why are high concentrations of myoinositol excreted into the urine of diabetic patients?
In healthy persons, myoinositol, like glucose, is almost completely reabsorbed in the renal tubules of the kidney, thus maintaining constant blood concentrations.2,9 However, when blood glucose increases, reabsorption of myoinositol in the renal tubules is inhibited by glucose, so myoinositol is excreted in urine.10
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Q5:
Does blood myoinositol change before and after glucose loading?
Yamagata et al. performed a 75-g OGTT in 146 subjects after obtaining informed consent to investigate correlations between glucose tolerance and changes in blood myoinositol before and after glucose loading. They found no significant differences in blood myoinositol concentrations among subjects with normal glucose tolerance, borderline type or diabetes mellitus.11
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Q6:
How can myoinositol be measured?
Myoinositol can be measured by gas chromatography or gas chromatography / mass spectrometry, but sample handling, including the need for pretreatment, is complex, and there problems exist with sensitivity and accuracy. "Lucica® MI" uses an enzyme assay (enzymatic cycling method) that provides good performance for sensitive and accurate measurements.12,13 With Lucica® MI, sample pretreatment is not necessary, and multiple samples can be measured using a biochemical autoanalyzer.
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Q7:
How is the myoinositol test performed
Urine samples are collected before (0 h) and 2 h after a 75-g glucose load to measure urinary myoinositol and creatinine (see Q9 "use of enzyme method”). Urinary myoinositol is adjusted for creatinine, and ΔUMI is calculated as the 2 h value minus the 0 h value. No drawing of blood is required, so testing can be performed in many patients simultaneously.
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Q8:
Is testing covered by insurance?
As of January 1, 2008, 120 NHI points have been approved for test reimbursement in Japan.
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Q9:
Is the creatinine analytical assay included in the kit?
The creatinine assay is not included in the kit and must be purchased separately. A creatinine assay from any manufacturer is acceptable, providing it is a highly specific enzyme assay. Chemical methods may yield results different from enzyme assay methods and should not be used.
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Q10:
Is glucose loading (75-g glucose load) always necessary?
Urinary myoinositol testing is designed to detect to impaired glucose tolerance (IGT) after glucose loading, so glucose loading must be performed. In preliminary evaluation using urine samples after a specified meal, good results similar to those after glucose loading have been reported.14 Testing with urine samples after a regular meal is currently being investigated.
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Q11:
Are two urine samples, before and after glucose loading, necessary?
Urinary myoinositol concentrations after fasting differ among individuals. The ΔUMI is an index of change in urinary myoinositol before and after glucose loading, so two urine samples are required.11
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Q12:
Is it necessary to add some type of preservative?
Preservatives may cause erroneous results for creatinine, which is measured simultaneously, and should be avoided.
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Reference

1) Toyota T: Key words for diabetes mellitus. Japan Medical Publisher 2rd version: 80, 2000.

2) Nakamura J, et al: Myoinositol. Nippon Rinsho 56: 129-134, 1998.

3) Clements RS, et al: Myoinositol in diabetes mellitus. Effect of insulin treatment. Diabetes 26: 215-221, 1977.

4) Nishizuka Y: Calcium, phospholipid turnover and transmembrane signaling. Philos Trans R Soc Lond B Biol Sci 302: 101-112, 1983.

5) Greene DA: Sorbitol, myo-inositol and sodium potassium ATPase in diabetic peripheral nerve. Drug 32(suppl 2): 6-14, 1986.

6) Vohl H: Ueber das Auftreten des Inosites im Haru bei Nierenkrankheiten und die Verwandlung des Diabetes inositus. Arch. F. physical. Hulk. Stuttg. N. F 2: 410-412, 1858.

7) Kawazu S, et al: Determination of urinary myoinositol: comparison of glucose intolerance group with normal type. Jpn J Med Pharm Sci 52(6): 981-987, 2004.

8) Greene DA, et al: Sorbitol, phosphoinositides, and sodium-potassium ATPase in the pathogenesis of diabetic complications. N Engl J Med 316: 599-606, 1987.

9) Clements RS, et al: The role of abnormal polyol metabolism in diabetic complication. In: Brodoff BN, Bleicher SJ, editors. Diabetes Mellitus and Obesity. Baltimore, London: Williams and Wilkins; 117-128, 1982.

10) Daughaday WH, et al: The renal excretion of inositol in normal and diabetic human beings. J Clin Invest 33: 326-332, 1954.

11) Yamagata F, et al: Determination of urinary myoinositol at 75g oral glucose tolerance test: comparisons of normal, borderline and diabetic types, and setting of cut-off value by ROC analysis. Jpn J Med Pharm Sci 52(6): 975-980, 2004.

12) Yamakoshi M, et al: Determination of urinary myo-inositol concentration by an improved enzymatic cycling method using myo-inositol dehydrogenase from Flavobacterium sp. Clin Chim Acta 328: 163-171, 2003.

13) Sarashina G, et al: A study of urinary myo-inositol as a sensitive marker of glucose intolerance. Clin Chim Acta 344: 181-188, 2004.

14) Kanauchi N, et al: Relation between myoinositol and glucose intolerance. Tounyoubyou 45(2): S-101, 2002.

 

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