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Cited by 144Aldose Reductase and TaurineMetabolism, Diabetes, and CancerDiet, Metabolism, and Disease

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls

Sun, Tie-hua, Heimark, Douglas B, Nguygen, Thang, Nadler, Jerry L, Larner, Joseph·2002·Biochemical and Biophysical Research Communications
DOI 10.1016/s0006-291x(02)00313-3
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Abstract

Previous data from our and other labs demonstrated a decreased chiro-inositol content in urine and tissues of human subjects and animals with type 2 diabetes. In urine this decrease in chiro-inositol was accompanied by an increase in myo-inositol content. Decreased urine levels of chiro-inositol in monkeys were next correlated with the severity of underlying insulin resistance determined by five separate assays. To investigate the decreased chiro-inositol and the accompanying increased myo-inositol excretions in urine in humans and monkeys, we postulated a defect in the epimerization of myo-inositol to chiro-inositol. [(3)H]Myo-inositol was then shown to be converted to [(3)H]chiro-inositol in rats in vivo and in fibroblasts in vitro in a process stimulated by insulin. We next demonstrated that the conversion of [(3)H]myo-inositol to [(3)H]chiro-inositol in vivo was markedly decreased in GK type 2 diabetic rats compared to Wistar controls in liver, muscle, and fat, insulin sensitive tissues. Decreases of 20-25% conversion to baseline levels of under 5% conversion were observed. In the present work, we initially compared the total contents of myo-inositol and chiro-inositol in GK type 2 diabetic rat kidney, liver, and muscle compared to Wistar controls. We demonstrated a consistent decreased total chiro-inositol to myo-inositol ratio in kidney, liver, and muscle compared to controls. We next established the presence of a myo-inositol to chiro-inositol epimerase activity in rat liver cytosol. Enzyme activity was shown to be time and enzyme concentration dependent with a broad pH optimum. It required NADH and NADPH for full activity, which is compatible with its action via an oxido-reductive mechanism. Lastly, we demonstrated that the epimerase enzyme bioactivity was significantly decreased in muscle, liver, and fat cytosolic extracts of GK type 2 diabetic rats versus Wistar controls. Decreased myo-inositol to chiro-inositol epimerase activity may therefore play a role in explaining the decreased chiro-inositol to myo-inositol urine and tissue ratios observed here and in previous animal and human studies. Further it may also possibly play a role in the underlying insulin resistance.

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Metadata

Authors
Sun, T.-H., Heimark, D. B., Nguygen, T., Nadler, J. L., & Larner, J.
Affiliations
  • Insmed (United States) (US)
  • University of Virginia Medical Center (US)
Corresponding author
Larner, Joseph
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2002-05
Volume
293
Issue
3
Pages
1092-1098
ISSN
0006-291X (ISSN-L)
DOI
10.1016/s0006-291x(02)00313-3
OpenAlex
W2081776150
Cited by
144
References
20
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 16 · 2022: 6 · 2021: 9 · 2020: 15 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 15 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 7
FWCI
0.12
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK055240)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
myo-inositol, chiro-inositol, epimerization, type 2 diabetes, insulin resistance, Goto-Kakizaki rats, liver cytosol, muscle, kidney, fats, NADPH-dependent enzyme
MeSH terms
Adipose Tissue, Animals, Cell Extracts, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Inositol, Kidney, Liver, Male, Rats, Mutant Strains, Sugar Alcohol Dehydrogenases, Rats, Wistar, Muscle, Skeletal, Rats

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