glucose transporter 1 deficiency

BACKGROUND AND AIMS: Stearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids into monounsaturated fatty acids and plays an important regulatory role in lipid metabolism. Previous studies have demonstrated that mice deficient in SCD1 are protected from diet-induced obesity and hepatic steatosis due to altered lipid esterification and increased energy expenditure. Previous studies in our lab have shown that intestinal SCD1 modulates intestinal and plasma lipids and alters cholesterol metabolism...

Psoriasis is a chronic and relapsing inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been identified as a cancer promoter in cutaneous squamous cell carcinoma by us, yet its role in psoriasis remains elusive. In this study, we report that LPCAT1 is highly expressed in psoriatic skin lesions. LPCAT1 promotes keratinocyte hyperproliferation and enhances the secretion of IL-1β, IL-6, CXCL10, CCL20, S100A9, and platelet-activating factor (PAF)...

Pro-inflammatory microglia mainly rely on glycolysis to maintain cytokine production during ischemia, accompanied by an increase in inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1). The role of energy metabolism in the pro-inflammatory response of microglia is currently unclear. In this study, we tested the response of microglia in mice after cerebral ischemia and simulated an energy environment in vitro using low glucose culture medium. The research results indicate that the expression levels of iNOS and arginase 1 (ARG1) increase in the ischemic mouse brain, but the upregulation of MCT1 expression is mainly present in iNOS positive microglia...

OBJECTIVE: NF1 is a tumor suppressor gene and its protein product, neurofibromin, is a negative regulator of the RAS pathway. NF1 is one of the top driver mutations in sporadic breast cancer such that 27% of breast cancers exhibit damaging NF1 alterations. NF1 loss-of-function is a frequent event in the genomic evolution of estrogen receptor (ER)+ breast cancer metastasis and endocrine resistance. Individuals with Neurofibromatosis type 1 (NF) - a disorder caused by germline NF1 mutations - have an increased risk of dying from breast cancer [1-4]...

Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions...

Glucose transporter type 1 deficiency syndrome (GLUT-1DS) is characterized by alterations in glucose translocation through the blood-brain barrier (BBB) due to mutation involving the GLUT-1 transporter. The fundamental therapy is ketogenic diet (KD) that provide an alternative energetic substrate - ketone bodies that across the BBB via MCT-1 - for the brain. Symptoms are various and include intractable seizure, acquired microcephalia, abnormal ocular movement, movement disorder, and neurodevelopment delay secondary to an energetic crisis for persistent neuroglycopenia...

Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1f/f Mb1Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation...

BACKGROUND/AIM: Intestinal lymphatic vessels (lacteals) play a critical role in the absorption and transport of dietary lipids into the circulation. Calcitonin gene-related peptide and receptor activity-modifying protein 1 (RAMP1) are involved in lymphatic vessel growth. This study aimed to examine the role of RAMP1 signaling in lacteal morphology and function in response to a high-fat diet (HFD). MATERIALS AND METHODS: RAMP1 deficient (RAMP1-/- ) or wild-type (WT) mice were fed a normal diet (ND) or HFD for 8 weeks...

Heart failure (HF) and chronic kidney disease (CKD) are associated with high mortality. In both disorders, impaired iron homeostasis, mostly in the form of a functional iron deficiency, is a frequent co-morbidity. In HF, functional iron deficiency and management by i.v. iron supplementation have been proven to affect both prognosis and functional capacity. In the same context, iron supplementation is routine for the adequate management of renal anemia in CKD. In numerous recent studies in HF and in CKD, sodium-glucose transporter 2 (SGLT2) inhibitor treatment has been proven to significantly reduce mortality...

The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is a pentameric protein complex localized at endosomes, where it facilitates the transport of numerous receptors from endosomes toward the plasma membrane. Recent studies have shown that the WASH complex plays an essential role in cholesterol and glucose homeostasis in humans and mice. To investigate the physiological importance of intestinal WASH, we ablated the WASH component WASHC1 specifically in murine enterocytes. Male and female intestine-specific WASHC1-deficient mice (Washc1IKO ) were challenged with either a standard chow diet or a high-cholesterol (1...

INTRODUCTION: Numerous studies demonstrated that NLRP3 has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) regulated the NLRP3 inflammasome, which has emerged as a novel therapeutic approach for treating IBD. OBJECTIVES: The exact role of NLRP3 in regulating MSCs' function is unclear. Our study aimed to explore how NLRP3 affects the therapeutic effects of MSCs in colitis. METHODS: We extracted MSCs from the bone marrow of C57/B6 mice and Nlrp3 KO mice, and identified them using differentiation assays and flow cytometry...

UNLABELLED: The neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-inducible factor 1 α (HIF-1 α), heat shock protein 70 (HSP-70), interleukin-17A (IL-17A), IL-35, vitamin D3 (VITD), glucose transporter-1 (GUT1), and AMP-activated protein kinase (AMPK) were estimated in Saudi ASD children versus age-matched neurotypical controls, aiming to investigate whether these parameters have potential roles in the pathophysiologic mechanisms of ASD and hoping to find a reliable marker for early ASD diagnosis...

BACKGROUND: Heart failure (HF) is a serious and frequent pathology. It represents a major public health problem. We have few data about this pathology in our country. The aim of our study is to determine the epidemiological, clinical, therapeutic, and prognostic characteristics of new-onset HF with reduced left ventricular ejection fraction (HFrEF) and to study the degree of conformity of the management of HF with international recommendations. RESULTS: Our study population includes 210 patients hospitalized for HFrEF newly diagnosed...

The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid β metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions...

BACKGROUND: Paediatric Huntington disease with highly expanded mutations (HE-PHD; >80 CAG repeats) presents atypically, compared to adult-onset Huntington disease (AOHD), with neurodevelopmental delay, epilepsy, abnormal brain glucose metabolism, early striatal damage, and reduced lifespan. Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD. METHODS: We compared GLUT-1 and GLUT-3 protein expression in HE-PHD, juvenile-onset (JOHD), and AOHD brains (n = 2; n = 3; n = 6) and periphery (n = 3; n = 2; n = 2) versus healthy adult controls (n = 6; n = 6)...

BACKGROUND AND AIMS: Vascular calcification (VC) is regarded as an independent risk factor for cardiovascular events in type 2 diabetic patients. Glucose transporter 1 (GLUT1) involves VC. Intermedin/Adrenomedullin-2 (IMD/ADM2) is a cardiovascular protective peptide that can inhibit multiple disease-associated VC. However, the role and mechanism of IMD in diabetic VC remain unclear. Here, we investigated whether IMD inhibits diabetic VC by inhibiting GLUT1. METHODS AND RESULTS: It was found that plasma IMD concentration was significantly decreased in type 2 diabetic patients and in fructose-induced diabetic rats compared with that in controls...

INTRODUCTION: Patients with type 1 diabetes (T1D) demonstrate brain alterations, including white matter lesions and cerebral atrophy. In this case-control study, we investigated if a reason for this atrophy could be because of diabetes-related complications affecting cerebrovascular or cerebral glycolytic functions. Cerebral physiological dysfunction can lead to energy deficiencies and, consequently, neurodegeneration. METHODS: We examined 33 patients with T1D [18 females, mean age: 50...

Mitochondria perform critical functions, including respiration, ATP production, small molecule metabolism, and anti-oxidation, and they are involved in a number of human diseases. While the mitochondrial genome contains a small number of protein-coding genes, the vast majority of mitochondrial proteins are encoded by nuclear genes. In fission yeast Schizosaccharomyces pombe , we screened 457 deletion ( del ) mutants deficient in nuclear-encoded mitochondrial proteins, searching for those that fail to form colonies in culture medium containing low glucose (0...

Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities...

BACKGROUND & AIMS: Metabolic reprogramming is essential for the activation and functions of macrophages, including bacterial killing and cytokine production. Bromodomain-containing protein 4 (BRD4) has emerged as a critical regulator of innate immune response. However, the potential role of BRD4 in metabolic reprogramming of macrophage activation upon H. pylori infection remains unclear. METHODS: Bone marrow-derived macrophages (BMDMs) from WT and Brd4-myeloid deletion conditional knockout mice (Brd4-CKO) were infected with H...