A5089891635- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Genetic and Kidney Cyst Diseases
- Metabolism, Diabetes, and Cancer
- FOXO transcription factor regulation
- Heat shock proteins research
- Diabetes Treatment and Management
- Diabetes Management and Research
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- MicroRNA in disease regulation
- Renal cell carcinoma treatment
- Extracellular vesicles in disease
- RNA modifications and cancer
- Exercise and Physiological Responses
- Pluripotent Stem Cells Research
- Dietary Effects on Health
- Diet and metabolism studies
- Diabetes and associated disorders
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Regulation of Appetite and Obesity
Kumamoto University
2011-2024
Joslin Diabetes Center
2016-2022
Harvard University
2016-2022
Complications of diabetes affect tissues throughout the body, including central nervous system. Epidemiological studies show that diabetic patients have an increased risk depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in brain or on hypothalamic neurons display array metabolic abnormalities; however, role action astrocytes neurobehaviors remains less well studied. Here, we demonstrate are a direct target knockout IR causes...
Abstract Despite a high degree of homology, insulin receptor (IR) and IGF-1 (IGF1R) mediate distinct cellular physiological functions. Here, we demonstrate how domain differences between IR IGF1R contribute to the functions these receptors using chimeric site-mutated receptors. Receptors with intracellular show increased activation Shc Gab-1 more potent regulation genes involved in proliferation, corresponding their higher mitogenic activity. Conversely, display IRS-1 phosphorylation,...
Interactions of diet, gut microbiota, and host genetics play important roles in the development obesity insulin resistance. Here, we have investigated molecular links between resistance, glucose metabolism 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet antibiotic treatment. Antibiotic treatment altered intestinal decreased tissue inflammation, improved signaling basal stimulated states, obesity- diabetes-prone C57BL/6J mice on a high-fat (HFD). Many...
Significance Circulating hormones must cross the vascular endothelium to elicit their actions in target tissues via either transcytosis or paracellular diffusion. Insulin receptors on endothelial cells are believed mediate of circulating insulin, but how this affects insulin action vivo is unknown. Here, we demonstrate that knockout delays kinetics activation signaling skeletal muscle, fat, and several regions brain not liver olfactory bulb. This alters induces tissue-specific resistance...
A major target of insulin signaling is the FoxO family Forkhead transcription factors, which translocate from nucleus to cytoplasm following insulin-stimulated phosphorylation. Here we show that factors FoxK1 and FoxK2 are also downstream targets action, but stimulation, they nucleus, reciprocal translocation FoxO1. FoxK1/FoxK2 dependent on Akt-mTOR pathway, while its localization in basal state GSK3. Knockdown liver cells results upregulation genes related apoptosis down-regulation involved...
The kidney develops through reciprocal interactions between two precursor tissues: the metanephric mesenchyme and ureteric bud. We previously demonstrated that zinc finger protein Sall1 is essential for bud attraction toward mesenchyme. Here, we show Kif26b , a kinesin family gene, downstream target of disruption this gene causes agenesis because impaired attraction. In -null metanephros, compact adhesion mesenchymal cells adjacent to buds polarized distribution integrin α8 were impaired,...
Significance Although there has been tremendous progress in understanding hormone action and its relationship to human physiology disease, no comprehensive approach search the viral genome for presence of human-like hormones. Here, using a bioinformatics approach, we have identified 16 different peptide hormones/growth factors, including four insulin/insulin growth factor (IGF)1-like peptides (VILPs) that homologous sequences viruses. When these VILPs were chemically synthesized, resulting...
Regulation of gene expression is an important aspect insulin action but in vivo intertwined with changing levels glucose and counter-regulatory hormones. Here we demonstrate that under euglycemic clamp conditions, physiological regulate interrelated networks more than 1,000 transcripts muscle liver. These include expected pathways related to lipid utilization, mitochondrial function, autophagy, as well unexpected pathways, such chromatin remodeling, mRNA splicing, Notch signaling. acutely...
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in gene encoding p85α regulatory subunit PI3K (PIK3R1) have been identified patients with SHORT syndrome — a disorder characterized by short stature, partial lipodystrophy, resistance. Here, we evaluated whether syndrome–associated PIK3R1 account for pathophysiology that underlies abnormalities generating knockin mice are heterozygous Pik3r1Arg649Trp...
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and have been shown to participate in almost every cellular process. Several miRNAs recently implicated glucose metabolism, but the roles of insulin-resistant conditions, such as obesity or type 2 diabetes, largely unknown. Herein, we focused on miR-222, which was increased livers high fat/high sucrose diet-fed mice injected with gold thioglucose (G+HFHSD). Overexpression miR-222 primary mouse...
Abstract Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes. To determine the relationship between these abnormalities, we created mice with muscle-specific knockout p110α or p110β catalytic subunits PI3K. We find that p110α, but not p110β, display impaired signaling reduced size due to enhanced proteasomal autophagic activity. Despite resistance atrophy, M-p110αKO show serum...
Kif26b, a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. Kif26b expression restricted to metanephric mesenchyme, and its transcription regulated by zinc finger transcriptional regulator Sall1. However, mechanism(s) which protein remain unknown. Here, we demonstrate phosphorylation subsequent polyubiquitination in developing kidney. We find that interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated 4...
Accumulation of visceral white adipose tissue (WAT) associates with insulin resistance, inflammation, and metabolic syndrome, whereas accumulation subcutaneous WAT may be protective. We aimed to identify molecular mechanisms that might provide mechanistic insights underlying the phenotypic differences in these tissues. Membrane Metallo-Endopeptidase (MME/Neprislyin) is an extracellular, membrane-bound protease enriched can target degradation a variety peptides, including insulin, IL6,...
Abstract Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation this central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role phosphatase binding Alpha4 (α4) that essential for serine/threonine 2A (PP2A) in insulin action/resistance adipocytes. Unexpectedly, adipocyte-specific inactivation α4 impairs insulin-induced Akt-mediated phosphorylation despite decrease levels. Interestingly, loss also reduces receptor tyrosine This...
Heat shock protein 72 (HSP72) is a major inducible molecule in the heat response that enhances intracellular stress tolerance. Decreased expression of HSP72 observed type 2 diabetes, which may contribute to development insulin resistance and chronic inflammation. We used knockout (HSP72-KO) mice investigate impact on glucose metabolism endoplasmic reticulum (ER) stress, particularly liver. Under high-fat diet (HFD) condition, HSP72-KO showed intolerance, resistance, impaired secretion,...
Adipose tissues, such as white, brown, and beige play pivotal roles in maintaining energy balance metabolic health. Whereas white adipocytes store energy, brown exhibit high expenditure owing to their distinct mitochondrial density UCP1 expression. Dysfunction these tissues contributes disorders type 2 diabetes cardiovascular diseases. tissue expansion through cell enlargement or increased numbers caused by excess storage substantially influences In obesity, hypertrophic trigger...