title: Protection by beta-Hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis.
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.
  
  
  CONCLUSIONS
  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.
authors: School of Biology, College of Science, University of Tehran, Tehran, Iran. sabokdast@ut.ac.ir.|Present address: Department of agronomy, and plant breeding, College of Agriculture & Natural Resources, University of Tehran, Karaj, Iran. sabokdast@ut.ac.ir.
authors: Manijheh
authors: M
authors: Sabokdast
authors: School of Biology, College of Science, University of Tehran, Tehran, Iran. mhabibi@ut.ac.ir.|Nano-Biomedicine Center of Excellence, Nanoscience and Nanotechnology Research Center, University of Tehran, Tehran, Iran. mhabibi@ut.ac.ir.
authors: Mehran
authors: M
authors: Habibi-Rezaei
authors: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. moosavi@ut.ac.ir.|Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran. moosavi@ut.ac.ir.
authors: Ali Akbar
authors: AA
authors: Moosavi-Movahedi
authors: School of Biology, College of Science, University of Tehran, Tehran, Iran. maryam.ferdousi@gmail.com.
authors: Maryam
authors: M
authors: Ferdousi
authors: School of Biology, College of Science, University of Tehran, Tehran, Iran. eazimirani@gmail.com.
authors: Effat
authors: E
authors: Azimzadeh-Irani
authors: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. poursasan_n@ibb.ut.ac.ir.
authors: Najmeh
authors: N
authors: Poursasan
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002942:Circular Dichroism; D006031:Glycosylation; D007328:Insulin / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes; D017628:Microglia / Q000187:drug effects*; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D008081:Liposomes; D020155:3-Hydroxybutyric Acid