RESUMEN
Background@#CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. @*Methods@#KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. @*Results@#CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). @*Conclusion@#Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.
RESUMEN
In both scotopic and photopic conditions, the rotation of a grating was found to elicit head movements in mice. The highest spatial frequency eliciting this optomotor response provided an estimate of visual acuity. In male C57BL/6J mice, visual acuity increased from 0.26cpd in scotopic conditions to 0.52cpd in photopic conditions whereas it was 0.52 cpd in both sets of conditions in 129/SvPas mice. No optomotor response was detected in albino CD1 mice and rd1 retinal degeneration mice although light sensitivity in CD1 mice was attested by photophobia and normal electroretinograms. This rapid and cheap method could provide a powerful test of visual performance in genetically modified and pharmacologically treated mice.
