title: Hyperketonemia decreases mitochondrial membrane potential and its normalization with chromium (III) supplementation in monocytes.
abstract: Altered cellular mitochondrial membrane potential (MMP) has been implicated in the increased insulin resistance and the risk for diabetes. Hyperketonemia is increasingly being identified in type 2 diabetic patients in addition to those with type 1 diabetes. No previous study has examined the effect of hyperketonemia and trivalent chromium on cellular mitochondrial membrane potential (MMP) in any cell type. Using a U937 monocyte cell culture model, this study examined the hypothesis that hyperketonemia decreases and trivalent chromium normalizes the cellular MMP level. Cells were cultured with control and ketone bodies [acetoacetate (AA), β-hydroxybutyrate (BHB)] in the absence or the presence (0.5-100 μM) of Cr(3+) at 37°C for 24 h. The MMP was determined using DiOC6 and flow cytometry. The results show a significant decrease in MMP in cells treated with AA, but not in the cells treated with BHB. The effect of AA on cellular MMP was prevented in chromium (III)-pretreated cells. Thus, hyperketonemia decreases the MMP, and supplementation with chromium (III) normalizes altered MMP, which may play a role in the improvement in glucose metabolism seen after chromium (III) supplementation in some studies with diabetic animals and patients.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Rains
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000090:Acetoacetates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements; D006801:Humans; D007662:Ketosis / Q000503:physiopathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009539:Nicotinic Acids / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000090:Acetoacetates; D009539:Nicotinic Acids; D009942:Organometallic Compounds; C102874:chromium nicotinic acid complex; D020155:3-Hydroxybutyric Acid