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Daru. 2015 Aug 27;23:42. doi: 10.1186/s40199-015-0126-5.

Protection by beta-Hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis.

Author information

1
School of Biology, College of Science, University of Tehran, Tehran, Iran. sabokdast@ut.ac.ir.
2
Present address: Department of agronomy, and plant breeding, College of Agriculture & Natural Resources, University of Tehran, Karaj, Iran. sabokdast@ut.ac.ir.
3
School of Biology, College of Science, University of Tehran, Tehran, Iran. mhabibi@ut.ac.ir.
4
Nano-Biomedicine Center of Excellence, Nanoscience and Nanotechnology Research Center, University of Tehran, Tehran, Iran. mhabibi@ut.ac.ir.
5
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. moosavi@ut.ac.ir.
6
Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran. moosavi@ut.ac.ir.
7
School of Biology, College of Science, University of Tehran, Tehran, Iran. maryam.ferdousi@gmail.com.
8
School of Biology, College of Science, University of Tehran, Tehran, Iran. eazimirani@gmail.com.
9
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. poursasan_n@ibb.ut.ac.ir.

Abstract

BACKGROUND:

Diabetes mellitus is characterized jointly by hyperglycemia and hyperinsulinemia that make insulin more prone to be glycated and evolve insulin advanced glycation end products (Insulin- AGE). Here, we report the effect of beta-hydroxy butyrate (BHB) (the predominant ketone body) on the formation of insulin-AGE, insulin glycation derived liposomal lipid peroxidation and insulin-AGE toxicity in microglial cells.

METHODS:

The inhibitory effect of BHB was monitored as a result of insulin incubation in the presence of glucose or fructose using AGE-dependent fluorescence, Tyr fluorescence as well as anilinonaphthalenesulfonate (ANS) andthioflavin T (ThT) binding, and circular dichroism (CD) investigations. To study lipid peroxidation induced by insulin glycation, thiobarbituric acid (TBA) assay and thiobarbituric acid reactive substance (TBARS) monitoring were used. The effect of insulin-AGE on microglial viability was investigated by 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) cell assay and Annexin V/propidium iodide (PI) staining.

RESULTS:

Here we are reporting the inhibitory effect of BHB on insulin glycation and generation of insulin-AGE as a possible explanation for insulin resistance. Moreover, the protective effect of BHB on consequential glycation derived liposomal lipid peroxidation as a causative event in microglial apoptosis is reported.

CONCLUSION:

The reduced insulin fibril formation, structural inertia to glycation involved conformational changes, anti-lipid peroxidation effect, and increasing microglia viability indicated the protective effect of BHB that disclose insight on the possible preventive effect of BHB on Alzheimer's disease.

PMID:
26311627
PMCID:
PMC4551523
DOI:
10.1186/s40199-015-0126-5
[Indexed for MEDLINE]
Free PMC Article

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