A5102990852- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Diabetes and associated disorders
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Trypanosoma species research and implications
- Diabetes Treatment and Management
- Cardiac Ischemia and Reperfusion
- Carbohydrate Chemistry and Synthesis
- Phytase and its Applications
- Pancreatitis Pathology and Treatment
- Biomedical Research and Pathophysiology
- Regulation of Appetite and Obesity
- Pluripotent Stem Cells Research
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Radioactive contamination and transfer
- Food composition and properties
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Graphite, nuclear technology, radiation studies
- Proteins in Food Systems
- Soybean genetics and cultivation
JCR Pharmaceuticals (Japan)
2018-2024
Kobe University
2010-2020
Chiba University
2000-2013
Foundation for Biomedical Research and Innovation
2010-2011
Foundation for Biomedical Research
2010-2011
Kyoto University Hospital
2003-2008
Toyohashi University of Technology
2006
Kyoto University
2005
Hokkaido University
2005
Kumamoto University
2002
Mucopolysaccharidosis II (MPS II) is an X-linked recessive lysosomal storage disease caused by mutations in the iduronate-2-sulfatase (IDS) gene. Since IDS catalyzes degradation of glycosaminoglycans (GAGs), deficiency this enzyme leads to accumulation GAGs most cells all tissues and organs, resulting severe somatic neurological disorders. Although replacement therapy with human (hIDS) has been used for treatment MPS II, not effective defects CNS mainly because cannot cross blood-brain...
Although several studies have suggested that insulin-secreting cells can be generated in vitro from residing adult exocrine pancreas, neither the origin of these nor their precise insulin secretory properties was obtained. We show here derived mouse pancreatic by suspension culture presence EGF and nicotinamide. The frequency insulin-positive only 0.01% initial preparation increased to ≈5% conditions. Analysis Cre/loxP-based direct cell lineage tracing system indicates newly made originate...
Expanding Sulfonylurea Mechanisms Sulfonylureas are important drugs used for treatment of diabetes that act through adenosine triphosphate–sensitive potassium channels to promote secretion insulin from the pancreas. Zhang et al. (p. 607 ) present another mechanism by which beneficial effects sulfonylureas may also be obtained. were identified in a screen substances modify activity Epac2, guanine nucleotide exchange factor small guanosine triphosphatase Rap1. Mice lacking Epac2 less...
Hunter syndrome (mucopolysaccharidosis II [MPS II]), a deficiency of iduronate-2-sulfatase (IDS), causes an accumulation glycosaminoglycans, giving rise to multiple systemic and CNS symptoms. The currently available therapies, idursulfase beta, are ineffective against the symptoms because they cannot pass blood-brain barrier (BBB). A novel IDS fused with anti-human transferrin receptor antibody (JR-141) has been shown penetrate BBB ameliorate learning deficits in model mice. This...
Glucose-induced insulin secretion from pancreatic β-cells depends critically on ATP-sensitive K+ channel (KATP channel) activity, but it is not known whether KATP channels are involved in the potentiation of by glucose-dependent insulinotropic polypeptide (GIP). In mice lacking (Kir6.2−/− mice), we found that pretreatment with GIP vivo failed to blunt rise blood glucose levels after oral load. Kir6.2−/− mice, was markedly attenuated, indicating essential effect GIP. contrast, glucagon-like...
Investigation of dietary therapy for diabetes has focused on meal size and composition; examination the effects sequence postprandial glucose management is limited. The fish or meat before rice excursion, gastric emptying incretin secretions were investigated.
By restoring glucose-regulated insulin secretion, glucagon-like peptide-1–based (GLP-1–based) therapies are becoming increasingly important in diabetes care. Normally, the incretins GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) jointly maintain normal blood glucose levels by stimulation of secretion pancreatic β cells. However, reason why only GLP-1–based drugs effective improving after presentation has not been resolved. ATP-sensitive K+ (KATP) channels play a crucial role...
We have established two sublines derived from the insulin-secreting mouse pancreatic β-cell line MIN6, designated m9 and m14. Cells exhibit glucose-induced insulin secretion in a concentration-dependent manner, whereas m14 cells respond poorly to glucose. In cells, glucose consumption lactate production are enhanced, ATP is largely through nonoxidative pathways. Moreover, dehydrogenase activity increased, hexokinase replaces glucokinase as glucose-phosphorylating enzyme. The ATP-sensitive K...
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 GLP-1 still needs be elucidated. Here we clarify effects human analog liraglutide on fate and function by using an inducible Cre/loxP-based tracing system alloxan-induced mice. Liraglutide was subcutaneously administered once daily for 30 days. The changes were...
Mucopolysaccharidosis II (MPS II), a lysosomal storage disease caused by mutations in iduronate-2-sulfatase (IDS), is characterized wide variety of somatic and neurologic symptoms. The currently approved intravenous enzyme replacement therapy with recombinant IDS (idursulfase) ineffective for CNS manifestations due to its inability cross the blood-brain barrier (BBB). Here, we demonstrate that clearance heparan sulfate (HS) deposited brain BBB-penetrable antibody-enzyme fusion protein...
ATP-sensitive potassium (K ATP ) channels are known to be critical in the control of both insulin and glucagon secretion, major hormones maintenance glucose homeostasis. The involvement K uptake target tissues insulin, however, is not known. We show here that Kir6.2(−/−) mice lacking Kir6.2, pore-forming subunit these channels, have no channel activity their skeletal muscles. A 2-deoxy-[ 3 H]glucose experiment vivo showed basal insulin-stimulated muscles adipose enhanced compared with...
Although application of the Edmonton protocol has markedly improved outcomes for pancreatic islet transplantation, insulin independence rate after transplantation from one donor pancreas proven to remain low. During isolation process and subsequent clinical islets are subjected severe adverse conditions that impair survival ultimately contribute graft failure. Pancreas preservation with two-layer method (TLM) improve transplant results by protecting isolated against apoptosis through...
Enzyme replacement therapy (ERT) improves somatic manifestations in mucopolysaccharidoses (MPS). However, because intravenously administered enzymes cannot cross the blood-brain barrier (BBB), ERT is ineffective against progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed patients with neuronopathic MPS. Attempts to surmount this problem have been made intrathecal intracerebroventricular order achieve CNS effects, but burdens on are inimical...
Mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by dysfunction of α-L-iduronidase (IDUA), is characterized the deposition dermatan sulfate (DS) and heparan (HS) throughout body, which causes several somatic central nervous symptoms. Although enzyme-replacement therapy (ERT) currently available to treat MPS I, it does not alleviate disorders, as cannot penetrate blood-brain barrier. Here we evaluate brain delivery, efficacy, safety JR-171, fusion protein comprising...
Mucopolysaccharidosis type I (MPS I) causes systemic accumulation of glycosaminoglycans due to a genetic deficiency α-L-iduronidase (IDUA), which results in progressive symptoms affecting multiple organs, including the central nervous system (CNS). Because blood-brain barrier (BBB) prevents enzymes from reaching brain, enzyme replacement therapy is effective only against somatic symptoms. Hematopoietic stem cell transplantation can address CNS symptoms, but risk complications limits its...
Insulin secretion from pancreatic β-cells occurs by sequential cellular processes, including glucose metabolism, electrical activity, Ca2+ entry, and regulated exocytosis. Abnormalities in any of these functions can impair insulin secretion. In the present study, we demonstrate that inhibition proteasome activity severely reduces mouse β-cell line MIN6-m9. Although no significant effects on metabolism ATP production were found presence inhibitors, both glucose- KCl-induced entry drastically...
Incretin/cyclic adenosine monophosphate (cAMP) signaling is critical for potentiation of insulin secretion. Although several cell lines pancreatic β-cells are currently available, there no suitable investigation incretin/cAMP signaling. In the present study, we have newly established β-cell (named MIN6-K) from IT6 mouse, which develops insulinoma. MIN6-K8 cells respond to both glucose and incretins, such as glucagon-like peptide-1 (GLP-1) glucose-dependent insulinotropic polypeptide (GIP),...