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Updated: Apr 5, 2026

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Published on: January 23, 2018
Protection by beta-Hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis
Manijheh Sabokdast1,2, Mehran Habibi-Rezaei3,4, Ali Akbar Moosavi-Movahedi5,6
1School of Biology, College of Science, University of Tehran, Tehran, Iran. sabokdast@ut.ac.ir.
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.
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