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Arthur Riggs Diabetes and Metabolism Re... Publications | LitMetric

132 results match your criteria: "Arthur Riggs Diabetes and Metabolism Research Institute[Affiliation]"

Diabetes results from an inadequate number of insulin-producing human beta cells. There is currently no clinically available effective means to restore beta cell mass in millions of people with diabetes. Although the DYRK1A inhibitors, either alone or in combination with GLP-1 receptor agonists (GLP-1) or transforming growth factor β (TGF-β) superfamily inhibitors (LY), induce beta cell replication and increase beta cell mass, the precise mechanisms of action remain elusive.

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Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types.

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Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as a promising therapeutic agent with a diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option in the clinic. Recent research has shed light on CBG's intriguing molecular mechanisms, highlighting its potential to modulate multiple physiological processes.

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Distinct RORγt-dependent Th17 immune responses are required for autoimmune pathogenesis and protection against bacterial infection.

Cell Rep

November 2024

Department of Immunology & Theranostics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. Electronic address:

T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor γ t (RORγt) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORγt impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium.

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Introduction: Double C2-like domain beta (DOC2B) is a vesicle priming protein critical for glucose-stimulated insulin secretion in β-cells. Individuals with type 1 diabetes (T1D) have lower levels of DOC2B in their residual functional β-cell mass and platelets, a phenotype also observed in a mouse model of T1D. Thus, DOC2B levels could provide important information on β-cell dys(function).

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Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration approval of teplizumab to delay disease development.

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Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance in mice by promoting insulin biogenesis and minimising beta cell apoptosis.

Diabetologia

January 2025

Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA.

Article Synopsis
  • * Research using genetically modified mice and human beta cells showed that increasing PAK1 in beta cells decreased cell death and boosted insulin production, especially under high-fat diet conditions.
  • * The results suggest that PAK1 enhances insulin gene expression and provides a protective effect against cell death, indicating its potential as a therapeutic target for improving beta cell function in diabetes.
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The maintenance of optimal glucose levels in the body requires a healthy reserve of the insulin producing pancreatic beta-cells. Depletion of this reserve due to beta-cell dysfunction and death results in development of diabetes. Recent findings highlight unresolved DNA damage as a key contributor to beta-cell defects in diabetes.

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Article Synopsis
  • Harmine, a key ingredient in the hallucinogenic drink Ayahuasca, raises questions about its psychoactive effects, maximum tolerated dose (MTD), and safety in humans when administered in pharmaceutical-grade form.
  • A Phase 1 trial with 25 healthy adults tested varying doses of harmine hydrochloride (100-500 mg) to assess safety and potential psychoactivity, identifying the MTD as between 100 and 200 mg while noting mild to moderate gastrointestinal and neurological side effects.
  • Results indicate that doses below 2.7 mg/kg of harmine HCl are generally safe with few adverse effects, while higher doses lead to more severe reactions and limited psychoactivity, marking this
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The Network for Pancreatic Organ Donors with Diabetes (nPOD) has helped shape the contemporary understanding of type 1 diabetes (T1D) pathogenesis in humans through the procurement, distribution to scientists, and collaborative study of human pancreata and disease-related tissues from organ donors with T1D and islet autoantibody positivity. Since its inception in 2007, nPOD has collected tissues from 600 donors, and these resources have been distributed across 22 countries to more than 290 projects, resulting in nearly 350 publications. Research projects supported by nPOD span the breadth of diabetes research, including studies on T1D immunology and β-cell biology, and have uniquely unveiled abnormalities in other pancreatic cell types.

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Background: Epigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac.

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Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial disease (PAD). Various types of cells, including but not limited to endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages (MΦs), play crucial roles in the pathogenesis of DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators that play important roles in cellular function, and their dysregulation in DM can contribute to PAD.

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Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.

Sci Transl Med

July 2024

Department of Molecular and Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.

Five hundred thirty-seven million people globally suffer from diabetes. Insulin-producing β cells are reduced in number in most people with diabetes, but most individuals still have some residual β cells. However, none of the many diabetes drugs in common use increases human β cell numbers.

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Update: the role of epigenetics in the metabolic memory of diabetic complications.

Am J Physiol Renal Physiol

September 2024

Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, California.

Diabetes, a chronic disease characterized by hyperglycemia, is associated with significantly accelerated complications, including diabetic kidney disease (DKD), which increases morbidity and mortality. Hyperglycemia and other diabetes-related environmental factors such as overnutrition, sedentary lifestyles, and hyperlipidemia can induce epigenetic changes. Working alone or with genetic factors, these epigenetic changes that occur without alterations in the underlying DNA sequence, can alter the expression of pathophysiological genes and impair functions of associated target cells/organs, leading to diabetic complications like DKD.

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Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.

Mol Metab

August 2024

Department of Internal Medicine and Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Background: Type 1 diabetes (T1D) is a complex multi-system disease which arises from both environmental and genetic factors, resulting in the destruction of insulin-producing pancreatic beta cells. Over the past two decades, human genetic studies have provided new insight into the etiology of T1D, including an appreciation for the role of beta cells in their own demise.

Scope Of Review: Here, we outline models supported by human genetic data for the role of beta cell dysfunction and death in T1D.

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Exocrine-to-endocrine cross talk in the pancreas is crucial to maintain β-cell function. However, the molecular mechanisms underlying this cross talk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of β-cells in vitro, but its physiological role in vivo in the pancreas is unknown.

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A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes.

Cell Rep Med

June 2024

Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS c/o Toscana Life Science, Siena, Italy; Tuscany Centre for Precision Medicine (CReMeP), Siena, Italy. Electronic address:

Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals.

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Article Synopsis
  • Scientists are trying to find better ways to check if tiny clusters of cells (islets) from donors are good enough before putting them into people with Type 1 diabetes.
  • They studied the genes related to low oxygen levels (hypoxia) in these islets from 85 donors to see how it affects transplantation results in mice.
  • The research showed that checking these hypoxia-related genes can help predict how well the transplant will work, which could be a faster method than the usual tests done in mice.
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Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up.

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4S-fluorination of ProB29 in insulin lispro slows fibril formation.

J Biol Chem

June 2024

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA. Electronic address:

Recombinant insulin is a life-saving therapeutic for millions of patients affected by diabetes mellitus. Standard mutagenesis has led to insulin variants with improved control of blood glucose; for instance, the fast-acting insulin lispro contains two point mutations that suppress dimer formation and expedite absorption. However, insulins undergo irreversible denaturation, a process accelerated for the insulin monomer.

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The role of bile acids in human aging.

Med Rev (2021)

April 2024

Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.

Bile acids are recognized as important signaling molecules that enable fine-tuned inter-communication from the liver, through the intestine, to virtually any organ, thus encouraging their pleiotropic physiological effects. Aging is a complex natural process defined as a progressive decline in cellular and organismal functions. A causal link between bile acids and the aging process is emerging.

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Identifying major histocompatibility complex class II-DR molecules in bovine and swine peripheral blood monocyte-derived macrophages using mAb-L243.

Vaccine

May 2024

Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Microbiology Department, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia. Electronic address:

Major histocompatibility complex class II (MHC-II) molecules are involved in immune responses against pathogens and vaccine candidates' immunogenicity. Immunopeptidomics for identifying cancer and infection-related antigens and epitopes have benefited from advances in immunopurification methods and mass spectrometry analysis. The mouse anti-MHC-II-DR monoclonal antibody L243 (mAb-L243) has been effective in recognising MHC-II-DR in both human and non-human primates.

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Objective: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy.

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It is crucial to study the human pancreas to understand the pathophysiological mechanisms associated with type 1 (T1D) and 2 diabetes (T2D) as well as the pancreas endocrine and exocrine physiology and interplay. Much has been learned from the study of isolated pancreatic islets, but this prevents examining their function and interactions in the context of the whole tissue. Pancreas slices provide a unique opportunity to explore the physiology of normal, inflamed, and structurally damaged islets within their native environment, in turn allowing the study of interactions between endocrine and exocrine compartments to better investigate the complex dynamics of pancreatic tissue.

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Transcriptome free energy can serve as a dynamic patient-specific biomarker in acute myeloid leukemia.

NPJ Syst Biol Appl

March 2024

The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew University of Jerusalem, P.O.B. 12272, Ein Kerem, Jerusalem, 91120, Israel.

Acute myeloid leukemia (AML) is prevalent in both adult and pediatric patients. Despite advances in patient categorization, the heterogeneity of AML remains a challenge. Recent studies have explored the use of gene expression data to enhance AML diagnosis and prognosis, however, alternative approaches rooted in physics and chemistry may provide another level of insight into AML transformation.

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