A5081308350- Pancreatic function and diabetes
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Nutrition and Health in Aging
- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Lipoproteins and Cardiovascular Health
- Mechanical and Optical Resonators
- Diet and metabolism studies
- Pancreatic and Hepatic Oncology Research
- Diet, Metabolism, and Disease
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Error Correcting Code Techniques
- Clinical Nutrition and Gastroenterology
- Adipokines, Inflammation, and Metabolic Diseases
- Advanced MEMS and NEMS Technologies
- Metabolism and Genetic Disorders
- Electron Spin Resonance Studies
- Muscle Physiology and Disorders
- FOXO transcription factor regulation
- Diabetes Management and Research
- Cancer-related Molecular Pathways
- Case Reports on Hematomas
Regeneron (United States)
2012-2025
Gifu University Hospital
2020-2022
Shiga University of Medical Science Hospital
2018
Kyoto University
2016-2017
Kyoto Pharmaceutical University
2014-2017
Shiga University of Medical Science
2011
Columbia University
2003-2005
Musashino Academia Musicae
1983
Proinsulin is a misfolding-prone protein, making its biosynthesis in the endoplasmic reticulum (ER) stressful event. Pancreatic β-cells overcome ER stress by activating unfolded protein response (UPR) and reducing insulin production. This suggests that transition between periods of high UPR-mediated recovery from cellular stress. We now report pseudotime ordering single humans without diabetes detected large-scale RNA sequencing. identified major states with 1) low UPR gene expression, 2) or...
Accelerated atherosclerosis is a major cause of morbidity and death in insulin-resistant states such as obesity the metabolic syndrome, but underlying mechanisms are poorly understood. We show that macrophages from obese (ob/ob) mice have increased binding uptake oxidized LDL, part due to post-transcriptional increase CD36 protein. Macrophages ob/ob also insulin resistant, shown by reduced expression signaling receptors. Three lines evidence indicate caused defective signaling: (a) Treatment...
Significance Pancreatic islets are complex structures composed of four cell types whose primary function is to maintain glucose homeostasis. Owing the scarcity and heterogeneity islet types, little known about their individual gene expression profiles. Here we used Fluidigm C1 platform obtain high-quality profiles each type from mice. We identified cell-type–specific transcription factors pathways providing previously unrecognized insights into genes characterizing cells. Unexpectedly, our...
Growth and differentiation factor 8 (GDF8) is a TGF-β superfamily member, negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent growth mice, but less impressive hypertrophy primates, including man. Broad suggests another family member negatively regulates mass, its blockade enhances seen with GDF8-specific inhibition. Here we show that activin A the long-sought second regulator. Activin specific inhibition, on top leads to pronounced force production mice monkeys....
Antagonizing glucagon action represents an attractive therapeutic option for reducing hepatic glucose production in settings of hyperglycemia where excess plays a key pathophysiological role. We therefore generated REGN1193, fully human monoclonal antibody that binds and inhibits receptor (GCGR) signaling vitro. REGN1193 administration to diabetic ob/ob diet-induced obese mice lowered blood levels observed GCGR-deficient mice. In mice, reduced food intake, adipose tissue mass, body weight....
The role of different tissues in insulin action and their contribution to the pathogenesis diabetes remain unclear. To examine this question, we have used genetic reconstitution experiments mice. Genetic ablation receptors causes early postnatal death from diabetic ketoacidosis. We show that combined restoration receptor function brain, liver, pancreatic β cells rescues knockout mice neonatal death, prevents a majority animals, normalizes adipose tissue content, lifespan, reproductive...
The role of different tissues in insulin action and their contribution to the pathogenesis diabetes remain unclear. To examine this question, we have used genetic reconstitution experiments mice. Genetic ablation receptors causes early postnatal death from diabetic ketoacidosis. We show that combined restoration receptor function brain, liver, pancreatic β cells rescues knockout mice neonatal death, prevents a majority animals, normalizes adipose tissue content, lifespan, reproductive...
Liver zonation characterizes the separation of metabolic pathways along lobules and is required for optimal function. Wnt/β-catenin signaling controls by activating genes in perivenous hepatocytes, while suppressing periportal counterparts. We now demonstrate that glucagon opposes actions on gene expression pattern. The effects were more pronounced hepatocytes where 28% all activated inhibited Wnt/β-catenin. receptors their are uniformly distributed not regulated opposing signal....
Inactivating mutations in the insulin receptor results extreme resistance. The resulting hyperglycemia is very difficult to treat, and patients are at risk for early morbidity mortality from complications of diabetes. We used antagonist S961 induce severe resistance, hyperglycemia, ketonemia mice. Using this model, we show that glucagon (GCGR) inhibition with a monoclonal antibody normalized blood glucose β-hydroxybutyrate levels. Insulin antagonism increased pancreatic β-cell mass...
Partial restoration of insulin receptor Insr expression in brain, liver, and pancreatic beta cells is sufficient for rescuing knockout mice from neonatal death, preventing diabetes ketoacidosis, normalizing life span reproductive function. However, the transgenically rescued (referred to as L1) have marked hyperinsulinemia, approximately 30% develop late-onset type 2 diabetes. Analyses protein indicated that L1 had modestly reduced content but normal insulin-stimulated Akt phosphorylation...
Partial restoration of insulin receptor Insr expression in brain, liver, and pancreatic β cells is sufficient for rescuing knockout mice from neonatal death, preventing diabetes ketoacidosis, normalizing life span reproductive function. However, the transgenically rescued (referred to as L1) have marked hyperinsulinemia, approximately 30% develop late-onset type 2 diabetes. Analyses protein indicated that L1 had modestly reduced content but normal insulin-stimulated Akt phosphorylation...
Trb3, a mammalian homolog of Drosophila tribbles, was proposed as suppressor Akt activity, predominantly in conditions fasting and diabetes. Given these prior studies, we sought to determine whether Trb3 plays major role modulating hepatic insulin sensitivity. To answer this question, produced mice which lacZ reporter knocked into the locus containing gene Trib3, resulting Trib3 null animal. expression analyses demonstrated that is expressed liver, adipose tissues, heart, kidney, lung, skin,...
Critical illness myopathy (CIM) is associated with severe skeletal muscle wasting and impaired function in intensive care unit (ICU) patients. The mechanisms underlying CIM remain incompletely understood. To elucidate the biological activities occurring at transcriptional level of ICU patients CIM, gene expression profiles, potential upstream regulators, enrichment pathways were characterized using RNA sequencing (RNA-seq). We also compared signatures genes perturbed by mechanical loading...
Rationale: Glucagon is a key hormone that regulates the adaptive metabolic responses to fasting. In addition maintaining glucose homeostasis, glucagon participates in regulation of cholesterol metabolism; however, molecular pathways underlying this effect are incompletely understood. Objective: We sought determine role hepatic Gcgr (glucagon receptor) signaling plasma and identify its mechanisms. Methods Results: show plays an essential LDL-C (low-density lipoprotein cholesterol) homeostasis...
Glucagon stimulates hepatic glucose production, in part by promoting the uptake and catabolism of amino acids. Inhibition liver glucagon receptor (GCGR) results elevated plasma acids, which triggers proliferation pancreatic alpha-cells, forming a liver-alpha cell loop. This study aims to delineate signaling molecules downstream GCGR mediate We knocked down GCGR, its G-coupled protein GNAS, two GNAS effectors, PKA EPAC2 (RAPGEF4). Mice with knockdown had similar suppression acid genes,...
<p dir="ltr">Glucagon stimulates hepatic glucose production, in part by promoting the uptake and catabolism of amino acids. Inhibition liver glucagon receptor (GCGR) results elevated plasma acids, which triggers proliferation pancreatic alpha-cells, forming a liver-alpha cell loop. This study aims to delineate signaling molecules downstream GCGR mediate We knocked down GCGR, its G-coupled protein GNAS, two GNAS effectors, PKA EPAC2 (RAPGEF4). Mice with knockdown had similar suppression...
<p dir="ltr">Glucagon stimulates hepatic glucose production, in part by promoting the uptake and catabolism of amino acids. Inhibition liver glucagon receptor (GCGR) results elevated plasma acids, which triggers proliferation pancreatic alpha-cells, forming a liver-alpha cell loop. This study aims to delineate signaling molecules downstream GCGR mediate We knocked down GCGR, its G-coupled protein GNAS, two GNAS effectors, PKA EPAC2 (RAPGEF4). Mice with knockdown had similar suppression...
Abstract Background Previous studies of mixed background mice have demonstrated that targeted deletion Vgf produces a lean, hypermetabolic mouse is resistant to diet-, lesion-, and genetically-induced obesity. To investigate potential mechanism(s) site(s) action VGF, neuronal endocrine secreted protein neuropeptide precursor, we further analyzed the metabolic phenotypes two independent VGF knockout lines on C57Bl6 backgrounds. Results Unlike hyperactive C57Bl6-129/SvJ background, homozygous...
Aging improves pancreatic β-cell function in mice. This is a surprising finding because aging typically associated with functional decline. We performed single-cell RNA sequencing of β-cells from 3- and 26-month-old mice to explore how changes gene expression contribute improved age. The old were healthy had reduced blood glucose levels increased mass, which correlated their body weight. β-Cells young similar transcriptome profiles. In fact, only 193 genes (0.89% all detected genes)...
This study was to assess the resting energy expenditure of patients with esophageal cancer using indirect calorimetry. Eight male and eight healthy controls were enrolled in this study. All underwent transthoracic esophagectomy lymph nodes dissections. The measured preoperatively, on postoperative day 7 14 Preoperatively, expenditure/body weight these significantly higher than that (23.3 ± 2.1 kcal/kg/day vs 20.4 1.6 kcal/kg/day), whereas measured/predicted from Harris-Benedict equation...
Plasma amino acids and their transporters constitute an important part of the feedback loop between liver pancreatic α-cell function, glucagon regulates hepatic acid turnover. Disruption receptor action activates results in high plasma hypersecretion associated with hyperplasia. In present study, we report a technique to rescue implanted human islets from mouse kidney capsule. Using this model, have demonstrated that expression transporter SLC38A4 increases α-cells after administration...