A5005604127- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Peroxisome Proliferator-Activated Receptors
- Protein Tyrosine Phosphatases
- Endoplasmic Reticulum Stress and Disease
- Diet and metabolism studies
- FOXO transcription factor regulation
- Protein Kinase Regulation and GTPase Signaling
- Lipid metabolism and biosynthesis
- PI3K/AKT/mTOR signaling in cancer
- Muscle metabolism and nutrition
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Receptor Mechanisms and Signaling
- Diet, Metabolism, and Disease
- Immune Cell Function and Interaction
- Neuropeptides and Animal Physiology
- Cardiovascular Disease and Adiposity
- Aortic aneurysm repair treatments
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Metabolomics and Mass Spectrometry Studies
Chungnam National University
2025
University of Massachusetts Chan Medical School
2015-2024
Seoul National University
2015-2024
Institute of Molecular Medicine
2010-2021
Diabetes Australia
2010-2021
Massachusetts Academy of Math and Science
2020
Biotechnology Institute
2016
Ohio University
2016
Yale University
2002-2013
National Institute of Environmental Health Sciences
2013
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps action include phosphorylation of scaffolding proteins activation phosphatidylinositol 3-kinase. These early events lead to the serine-threonine protein kinase Akt, also known as B. We show that mice deficient Akt2 are impaired ability lower blood glucose because defects hormone liver skeletal muscle. data establish an essential gene maintenance normal homeostasis.
Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking activation of receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism which mediate this effect, rats were infused with either a lipid emulsion (consisting mostly 18:2 acids) or glycerol. Intracellular C18:2 CoA increased time-dependent fashion, reaching an ∼6-fold elevation 5 h, whereas there was no change concentration any other...
Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine that has been implicated in the regulation of insulin action, as well other signal transduction pathways. To investigate role PTP-1B vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient have remarkably low adiposity and are protected from diet-induced obesity. Decreased due to marked reduction fat cell mass without decrease adipocyte number. Leanness accompanied increased basal...
Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims the current study are to evaluate role FGF21 in energy metabolism provide mechanistic insights into its lipid-lowering effects a high-fat diet-induced obesity (DIO) model.DIO or normal lean mice were treated with vehicle recombinant murine FGF21. Metabolic parameters including body weight, glucose, levels monitored, hepatic gene expression was analyzed. Energy insulin...
Insulin resistance in skeletal muscle and liver may play a primary role the development of type 2 diabetes mellitus, mechanism by which insulin occurs be related to alterations fat metabolism. Transgenic mice with muscle- liver-specific overexpression lipoprotein lipase were studied during 2-h hyperinsulinemic-euglycemic clamp determine effect tissue-specific increase on action signaling. Muscle-lipoprotein had 3-fold triglyceride content resistant because decreases insulin-stimulated...
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation serine kinase cascade involving IKK-β. To test this hypothesis, we first examined insulin action signaling awake rats during hyperinsulinemic-euglycemic clamps after lipid infusion with or without pretreatment salicylate, known inhibitor Whole-body glucose uptake metabolism were estimated using [3-3H]glucose infusion, individual tissues was [1-14C]2-deoxyglucose injection clamp....
In lipoatrophic diabetes, a lack of fat is associated with insulin resistance and hyperglycemia. This in striking contrast to the usual association diabetes obesity. To understand underlying mechanisms, we transplanted adipose tissue into A-ZIP/F-1 mice, which have severe form diabetes. Transplantation wild-type reversed hyperglycemia, dramatically lowered levels, improved muscle sensitivity, demonstrating that mice caused by tissue. All aspects phenotype including hyperphagia, hepatic...
Macrophage JNK in Metabolic Disease Inflammation is thought to be an important driver of diet-induced obesity and insulin resistance. Proinflammatory, M1 phenotype macrophages the c-jun NH 2 terminal kinases (JNK) are central players this process. But whether expression specifically required inside unclear. In mice containing a macrophage-specific deletion both Jnk1 Jnk2 , Han et al. (p. 218 published online 6 December; see Perspective by Ferrante Jr. ) found that were protected against many...
Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant sites are difficult to identify in cultured cells and validate isolated tissues. Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates at Ser307, which inhibits insulin-stimulated tyrosine IRS-1. To monitor Ser307 various cell tissue backgrounds, prepared a phosphospecific polyclonal antibody designated αpSer307. This revealed TNF-α, IGF-1, or stimulated 3T3-L1 preadipocytes...
A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development insulin resistance. JNK1 is therefore a potential target for therapeutic treatment metabolic syndrome. We explored mechanism signaling by engineering mice in which Jnk1 gene was ablated selectively adipose tissue. deficiency tissue suppressed diet-induced resistance liver. JNK1-dependent secretion inflammatory cytokine interleukin-6 caused increased expression liver SOCS3,...
The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine role IL-6 development insulin resistance, we examined effects treatment on whole-body action glucose metabolism vivo during hyperinsulinemic-euglycemic clamps awake mice. Pretreatment blunted insulin's ability to suppress hepatic production insulin-stimulated receptor substrate...
Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations fat metabolism. Recent studies have suggested that local accumulation metabolites inside skeletal muscle activate serine kinase cascade involving protein C–θ (PKC-θ), leading defects insulin signaling glucose transport muscle. To test this hypothesis, we examined whether mice with inactivation PKC-θ are protected from fat-induced Skeletal hepatic action as assessed during...
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may be related to alterations fat metabolism. Fatless mice have been created using dominant-negative protein (A-ZIP/F-1) targeted gene expression adipocyte shown develop diabetes. To understand mechanism responsible for insulin these mice, we conducted hyperinsulinemic-euglycemic clamps awake fatless wild littermates before development examined action signaling muscle liver. We found severely insulin-resistant,...
OBJECTIVE Insulin resistance is a major characteristic of type 2 diabetes and causally associated with obesity. Inflammation plays an important role in obesity-associated insulin resistance, but the underlying mechanism remains unclear. Interleukin (IL)-10 anti-inflammatory cytokine lower circulating levels obese subjects, acute treatment IL-10 prevents lipid-induced resistance. We examined glucose homeostasis using transgenic mice muscle-specific overexpression (MCK-IL10). RESEARCH DESIGN...
Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations fat metabolism. Recent studies have suggested that local accumulation metabolites inside skeletal muscle activate serine kinase cascade involving protein C–θ (PKC-θ), leading defects insulin signaling glucose transport muscle. To test this hypothesis, we examined whether mice with inactivation PKC-θ are protected from fat-induced Skeletal hepatic action as assessed during...
Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, fails suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element-binding protein (ChREBP), transcriptional activator of glycolytic and lipogenic genes, plays central role paradox....
Peripheral insulin resistance and impaired action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs muscle, where glucose disposal response to is impaired. We have developed a transgenic mouse with dominant-negative insulin-like growth factor-I receptor (KR–IGF-IR) specifically targeted skeletal muscle. Expression KR–IGF-IR resulted formation hybrid receptors between mutant endogenous IGF-I receptors, thereby abrogating normal...
Obesity and insulin resistance in skeletal muscle are two major factors the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation receptor gene (MIRKO) normoglycemic but have increased fat mass. To identify potential mechanism for this important association, we examined action specific tissues MIRKO control mice under hyperinsulinemic-euglycemic conditions. We found that insulin-stimulated glucose transport glycogen synthesis were decreased by about 80% mice, whereas was...
Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose lipid metabolism in multiple organs. To understand the complex series of events that occur during development obesity-associated diabetes, we examined temporal pattern changes action individual organs chronic high-fat feeding C57BL/6 mice. Insulin-stimulated cardiac was significantly reduced after 1.5 weeks feeding, associated with blunted Akt-mediated signaling GLUT4 levels. Insulin skeletal...
The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling; consequently, mice deficient in are hypersensitive to insulin. Because PTP1B(-/-) have diminished fat stores, the extent which directly regulates glucose homeostasis unclear. Previously, we showed that brain-specific protected against high-fat diet-induced obesity and intolerance, whereas muscle-specific increased sensitivity independent changes adiposity. Here studied role liver lipid metabolism.We analyzed...