Domain induced budding in buckling membranes(Poster session 1, New Frontiers in Colloidal Physics : A Bridge between Micro- and Macroscopic Concepts in Soft Matter)

この論文は国立情報学研究所の電子図書館事業により電子化されました。この研究において、私たちは2成分からなるやわらかい平面的な膜を想定し、その膜面上での相分離現象とバックリング現象とがカップルしたモデルを提案する。また、数値シミュレーションなどを用いて、そのダイナミクスや平衡状態について調べる

Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice.

Glucagon-like peptide-1 (GLP-1) receptor agonists potentiate glucose-induced insulin secretion. In addition, they have been reported to increase pancreatic beta cell mass in diabetic rodents. However, the precise mode of action of GLP-1 receptor agonists still needs to be elucidated. Here we clarify the effects of the human GLP-1 analog liraglutide on beta cell fate and function by using an inducible Cre/loxP-based pancreatic beta cell tracing system and alloxan-induced diabetic mice. Liraglutide was subcutaneously administered once daily for 30 days. The changes in beta cell mass were examined as well as glucose tolerance and insulin secretion. We found that chronic liraglutide treatment improved glucose tolerance and insulin response to oral glucose load. Thirty-day treatment with liraglutide resulted in a 2-fold higher mass of pancreatic beta cells than that in vehicle group. Liraglutide increased proliferation rate of pancreatic beta cells and prevented beta cells from apoptotic cells death. However, the relative abundance of YFP-labeled beta cells to total beta cells was no different before and after liraglutide treatment, suggesting no or little contribution of neogenesis to the increase in beta cell mass. Liraglutide reduced oxidative stress in pancreatic islet cells of alloxan-induced diabetic mice. Furthermore, the beneficial effects of liraglutide in these mice were maintained two weeks after drug withdrawal. In conclusion, chronic liraglutide treatment improves hyperglycemia by ameliorating beta cell mass and function in alloxan-induced diabetic mice

Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses

Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various physiological processes, including cell signaling and organ development. Thus, inherited mutations of genes associated with the biosynthesis or degradation of HS can cause various diseases, particularly those involving the bones and central nervous system (CNS). Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders involving GAG accumulation throughout the body caused by a deficiency of GAG-degrading enzymes. GAGs are stored differently in different types of MPSs. Particularly, HS deposition is observed in patients with MPS types I, II, III, and VII, all which involve progressive neuropathy with multiple CNS system symptoms. While therapies are available for certain symptoms in some types of MPSs, significant unmet medical needs remain, such as neurocognitive impairment. This review presents recent knowledge on the pathophysiological roles of HS focusing on the pathogenesis of MPSs. We also discuss the possible use and significance of HS as a biomarker for disease severity and therapeutic response in MPSs

Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis

Enzyme replacement therapy (ERT) has paved the way for treating the somatic symptoms of lysosomal storage diseases (LSDs), but the inability of intravenously administered enzymes to cross the blood–brain barrier (BBB) has left the central nervous system (CNS)-related symptoms of LSDs largely impervious to the therapeutic benefits of ERT, although ERT via intrathecal and intracerebroventricular routes can be used for some neuronopathic LSDs (in particular, mucopolysaccharidoses). However, the considerable practical issues involved make these routes unsuitable for long-term treatment. Efforts have been made to modify enzymes (e.g., by fusing them with antibodies against innate receptors on the cerebrovascular endothelium) so that they can cross the BBB via receptor-mediated transcytosis (RMT) and address neuronopathy in the CNS. This review summarizes the various scientific and technological challenges of applying RMT to the development of safe and effective enzyme therapeutics for neuronopathic mucopolysaccharidoses; it then discusses the translational and methodological issues surrounding preclinical and clinical evaluation to establish RMT-applied ERT

Pancreatic beta cell mass and alpha cell mass.

<p>(<b>a</b>) Insulin/glucagon (upper), insulin/Pdx1 (middle), and insulin/FoxO1 (bottom) double immunostaining. Representative images of islets are shown. Scale bars, 100 μm. (<b>b</b>) Beta cell mass. Alloxan treatment markedly decreased beta cell mass. The beta cell mass was two-fold higher in liraglutide-treated mice than that in vehicle-treated mice on day 30. (<b>c</b>) Alpha cell mass. Alpha cell mass did not change by alloxan treatment. Liraglutide did not affect alpha cell mass. White bars represent vehicle-treated group (Veh) (n = 4–9), and black bars represent liraglutide-treated group (Lir) (n = 4–9). *<i>p</i> < 0.05</p

Evaluation of beta cell neogenesis.

<p>Double immunostaining for insulin (green) and YFP (red) indicates that pancreatic beta cells were specifically labeled by YFP. Scale bars, 100 μm. Quantification of YFP-labeled beta cells shows that the labeling index did not differ before and after liraglutide treatment. Veh, vehicle-treated group; Lir, liraglutide-treated group. Data are means ± SEM of five mice in each group. NS, difference not significant.</p