4,682 results match your criteria islet dysfunction


Type I interferons as key players in pancreatic β-cell dysfunction in type 1 diabetes.

Int Rev Cell Mol Biol 2021 23;359:1-80. Epub 2021 Mar 23.

Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, Elche, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet inflammation (insulitis) and specific pancreatic β-cell destruction by an immune attack. Although the precise underlying mechanisms leading to the autoimmune assault remain poorly understood, it is well accepted that insulitis takes place in the context of a conflicting dialogue between pancreatic β-cells and the immune cells. Moreover, both host genetic background (i. Read More

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Temporal metabolic and transcriptomic characteristics crossing islets and liver reveal dynamic pathophysiology in diet-induced diabetes.

iScience 2021 Apr 5;24(4):102265. Epub 2021 Mar 5.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

To investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for insulin secretion (islets) and action (liver) every 4 weeks in mice on high-fat (HFD) or chow diet for 24 weeks, linking to longitudinal profile of metabolic characteristics. The diverse responses of α, β, and δ cells to glucose and palmitate indicated HFD-induced dynamic deterioration of islet function from dysregulation to failure. Insulin resistance developed with variable time course in different tissues. Read More

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The pancreatic islet: a micro-organ in control.

CellR4 Repair Replace Regen Reprogram 2021 19;9. Epub 2021 Mar 19.

Department of Surgery, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

The islets of Langerhans constitute the endocrine pancreas which regulates blood glucose homeostasis and their dysfunction results in diabetes. Each of the pancreatic islets constitutes an entire micro-organ with intricate cell to cell interactions and that is well vascularized and innervated. An important therapeutic advantage in islet transplant is that pancreatic islets maintain their organ integrity when isolated and transplanted to patients with severe diabetes. Read More

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Inherent Beta Cell Dysfunction Contributes to Autoimmune Susceptibility.

Biomolecules 2021 Mar 30;11(4). Epub 2021 Mar 30.

Barbara Davis Center for Diabetes, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.

The pancreatic beta cell is a highly specialized cell type whose primary function is to secrete insulin in response to nutrients to maintain glucose homeostasis in the body. As such, the beta cell has developed unique metabolic characteristics to achieve functionality; in healthy beta cells, the majority of glucose-derived carbons are oxidized and enter the mitochondria in the form of pyruvate. The pyruvate is subsequently metabolized to induce mitochondrial ATP and trigger the downstream insulin secretion response. Read More

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C-Peptide as a Therapy for Type 1 Diabetes Mellitus.

Biomedicines 2021 Mar 8;9(3). Epub 2021 Mar 8.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered. Read More

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Combination of human tau and islet amyloid polypeptide exacerbates metabolic dysfunction in transgenic mice.

J Pathol 2021 Apr 2. Epub 2021 Apr 2.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.

Amyloid plaques and neurofibrillary tangles composed of hyperphosphorylated tau are important contributors to Alzheimer's disease (AD). Tau also impacts pancreatic beta cell function and glucose homeostasis. Amyloid deposits composed of islet amyloid polypeptide (IAPP) are a pathological feature of type 2 diabetes (T2D). Read More

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A Dual Systems Genetics Approach Identifies Common Genes, Networks, and Pathways for Type 1 and 2 Diabetes in Human Islets.

Front Genet 2021 10;12:630109. Epub 2021 Mar 10.

Department of Translational T1D Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Type 1 and 2 diabetes (T1/2D) are complex metabolic diseases caused by absolute or relative loss of functional β-cell mass, respectively. Both diseases are influenced by multiple genetic loci that alter disease risk. For many of the disease-associated loci, the causal candidate genes remain to be identified. Read More

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Lessons from Human Islet Transplantation Inform Stem Cell-Based Approaches in the Treatment of Diabetes.

Front Endocrinol (Lausanne) 2021 11;12:636824. Epub 2021 Mar 11.

Department of Pediatrics, School of Medicine, University of Minnesota, Minneapolis, MN, United States.

Diabetes mellitus is characterized by the body's inability to control blood glucose levels within a physiological range due to loss and/or dysfunction of insulin producing beta cells. Progressive beta cell loss leads to hyperglycemia and if untreated can lead to severe complications and/or death. Treatments at this time are limited to pharmacologic therapies, including exogenous insulin or oral/injectable agents that improve insulin sensitivity or augment endogenous insulin secretion. Read More

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Proinsulin:C-peptide ratio trajectories over time in relatives at increased risk of progression to type 1 diabetes.

J Transl Autoimmun 2021 19;4:100089. Epub 2021 Feb 19.

University of Colorado Denver School of Medicine - the Barbara Davis Center for Diabetes, Aurora, CO, USA.

Objective: Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes. The ratio of proinsulin to C-peptide (PI:C ratio), has been proposed as a biomarker of beta cell dysfunction and is associated with progression to type 1 diabetes. However, relationships between PI:C ratios and autoantibody type and number have not been examined. Read More

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February 2021

Nifuroxazide improves insulin secretion and attenuates high glucose-induced inflammation and apoptosis in INS-1 cells.

Eur J Pharmacol 2021 Mar 18;899:174042. Epub 2021 Mar 18.

Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. Electronic address:

Inflammation and oxidative stress are important factors that cause islet β-cell dysfunction. STAT3 is not only a major factor in cell proliferation and differentiation, but also plays an important role in mediating inflammation. As a potent inhibitor of STAT3, the effect of Nifuroxazide (Nifu) on pancreatic islet cells in a high glucose environment has not been reported. Read More

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Single-cell RNA sequencing for engineering and studying human islets.

Curr Opin Biomed Eng 2020 Dec 4;16:27-33. Epub 2020 Jul 4.

Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Campus Box 8127, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

The islets of Langerhans are complex tissues composed of several cell types that secrete hormones. Loss or dysfunction of the insulin-producing β cells leads to dysregulation of blood glucose levels, resulting in diabetes. A major goal in cellular engineering has been to generate β cells from stem cells for use in cell-based therapies. Read More

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December 2020

Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant.

Sci Rep 2021 Mar 16;11(1):6014. Epub 2021 Mar 16.

Kidney Division, Transplantation Research Center, Harvard Medical School, Brigham and Women's Hospital, Boston, USA.

New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. Read More

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Evidence for the existence and potential roles of intra-islet glucagon-like peptide-1.

Islets 2021 Mar 16;13(1-2):32-50. Epub 2021 Mar 16.

Alberta Diabetes Institute, Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Glucagon-Like Peptide-1 (GLP-1) is an important peptide hormone secreted by L-cells in the gastrointestinal tract in response to nutrients. It is produced by the differential cleavage of the proglucagon peptide. GLP-1 elicits a wide variety of physiological responses in many tissues that contribute to metabolic homeostasis. Read More

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Association between glucose fluctuation during 2-hour oral glucose tolerance test, inflammation and oxidative stress markers, and β-cell function in a Chinese population with normal glucose tolerance.

Ann Transl Med 2021 Feb;9(4):327

Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Backgrounds: Glucose fluctuation (GF) may have detrimental effects in individuals with diabetes; however, clinical data on the association between short-term GF, inflammation/oxidative stress markers, and islet β-cell function based on a population with normal glucose tolerance (NGT) are insufficient. Therefore, we aimed to explore these associations in a Chinese population of 209 individuals with NGT in a cross-sectional analysis.

Methods: Individuals were categorized based on GF tertiles, calculated as the maximum-minimum glucose levels among four time points (0, 30, 60, 120 min) during 2-hour oral glucose tolerance test (OGTT). Read More

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February 2021

Rat prostaglandin EP3 receptor is highly promiscuous and is the sole prostanoid receptor family member that regulates INS-1 (832/3) cell glucose-stimulated insulin secretion.

Pharmacol Res Perspect 2021 Apr;9(2):e00736

Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA.

Chronic elevations in fatty acid metabolites termed prostaglandins can be found in circulation and in pancreatic islets from mice or humans with diabetes and have been suggested as contributing to the β-cell dysfunction of the disease. Two-series prostaglandins bind to a family of G-protein-coupled receptors, each with different biochemical and pharmacological properties. Prostaglandin E receptor (EP) subfamily agonists and antagonists have been shown to influence β-cell insulin secretion, replication, and/or survival. Read More

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Lin28a ameliorates glucotoxicity-induced beta cell dysfunction and apoptosis.

BMB Rep 2021 Mar 11. Epub 2021 Mar 11.

Division of Biotechnology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.

An excessive and prolonged increase in glucose levels causes β-cell dysregulation, which is accompanied by impaired insulin synthesis and secretion, a condition known as glucotoxicity. Although it is known that both Lin28a and Lin28b regulate glucose metabolism, other molecular mechanisms that may protect against glucotoxicity are poorly understood. We investigated whether Lin28a overexpression can improve glucotoxicity-induced β-cell dysregulation in INS-1 and primary rat islet cells. Read More

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Unique human and mouse β-cell senescence-associated secretory phenotype (SASP) reveal conserved signaling pathways and heterogeneous factors.

Diabetes 2021 Mar 5. Epub 2021 Mar 5.

Joslin Diabetes Center, Section on Islet Cell and Regenerative Biology, Boston, MA, 02215

The aging of pancreatic β-cells may undermine their ability to compensate for insulin resistance, leading to the development of type 2 diabetes (T2D). Aging β-cells acquire markers of cellular senescence and develop a senescence-associated secretory phenotype (SASP) that can lead to senescence and dysfunction of neighboring cells through paracrine actions, contributing to β-cell failure. Herein, we defined the β-cell SASP signature based on unbiased proteomic analysis of conditioned media of cells obtained from mouse and human senescent β-cells and a chemically-induced mouse model of DNA damage capable of inducing SASP. Read More

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Human Islet Microtissues as an In Vitro and an In Vivo Model System for Diabetes.

Int J Mol Sci 2021 Feb 11;22(4). Epub 2021 Feb 11.

The Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska Sjukhuset L1:03, 17176 Stockholm, Sweden.

Loss of pancreatic β-cell function is a critical event in the pathophysiology of type 2 diabetes. However, studies of its underlying mechanisms as well as the discovery of novel targets and therapies have been hindered due to limitations in available experimental models. In this study we exploited the stable viability and function of standardized human islet microtissues to develop a disease-relevant, scalable, and reproducible model of β-cell dysfunction by exposing them to long-term glucotoxicity and glucolipotoxicity. Read More

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February 2021

Cell-Free DNA Fragments as Biomarkers of Islet β-Cell Death in Obesity and Type 2 Diabetes.

Int J Mol Sci 2021 Feb 21;22(4). Epub 2021 Feb 21.

Kovler Diabetes Center and the Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.

Type 2 diabetes (T2D) typically occurs in the setting of obesity and insulin resistance, where hyperglycemia is associated with decreased pancreatic β-cell mass and function. Loss of β-cell mass has variably been attributed to β-cell dedifferentiation and/or death. In recent years, it has been proposed that circulating epigenetically modified DNA fragments arising from β cells might be able to report on the potential occurrence of β-cell death in diabetes. Read More

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February 2021

Piperine protects against pancreatic β-cell dysfunction by alleviating macrophage inflammation in obese mice.

Life Sci 2021 Jun 2;274:119312. Epub 2021 Mar 2.

Department of Pharmacology, School of Pharmacy, No. 308, Ningxia road, Qingdao University, Qingdao 266021, China. Electronic address:

Aims: Piperine, the major pharmacological ingredient of pepper, can delay the procession of "obesity to diabetes". However, the underlying mechanism remains unclear. This study aims to investigate whether piperine protects against β-cell dysfunction by inhibiting macrophage accumulation and M-like polarization. Read More

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Long Non-Coding RNAs as Key Modulators of Pancreatic β-Cell Mass and Function.

Front Endocrinol (Lausanne) 2020 8;11:610213. Epub 2021 Feb 8.

Section of Cell Biology and Functional Genomics, Division of Diabetes Endocrinology and Diabetes, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.

Numerous studies have sought to decipher the genetic and other mechanisms contributing to β-cell loss and dysfunction in diabetes mellitus. However, we have yet to fully understand the etiology of the disease or to develop satisfactory treatments. Since the majority of diabetes susceptibility are mapped to non-coding regions within the genome, understanding the functions of non-coding RNAs in β-cell biology might provide crucial insights into the pathogenesis of type 1 (T1D) and type 2 (T2D) diabetes. Read More

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February 2021

Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats.

Oxid Med Cell Longev 2021 2;2021:8833467. Epub 2021 Feb 2.

Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. Read More

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February 2021

Mesenchymal stromal cell-mediated immune regulation: A promising remedy in the therapy of type 2 diabetes mellitus.

Stem Cells 2021 Feb 23. Epub 2021 Feb 23.

State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases,Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China.

Type 2 diabetes mellitus (T2DM) is a major threat to global public health, with increasing prevalence as well as high morbidity and mortality, to which immune dysfunction has been recognized as a crucial contributor. Mesenchymal stromal cells (MSCs), obtained from various sources and possessing potent immunomodulatory abilities, have displayed great therapeutic potential for T2DM. Interestingly, the immunomodulatory capabilities of MSCs are endowed and plastic. Read More

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February 2021

Cell Heterogeneity and Paracrine Interactions in Human Islet Function: A Perspective Focused in β-Cell Regeneration Strategies.

Front Endocrinol (Lausanne) 2020 3;11:619150. Epub 2021 Feb 3.

Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

The β-cell regeneration field has shown a strong knowledge boost in the last 10 years. Pluripotent stem cell differentiation and direct reprogramming from other adult cell types are becoming more tangible long-term diabetes therapies. Newly generated β-like-cells consistently show hallmarks of native β-cells and can restore normoglycemia in diabetic mice in virtually all recent studies. Read More

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February 2021

Imeglimin amplifies glucose-stimulated insulin release from diabetic islets via a distinct mechanism of action.

PLoS One 2021 19;16(2):e0241651. Epub 2021 Feb 19.

Poxel SA, Lyon, France.

Pancreatic islet β-cell dysfunction is characterized by defective glucose-stimulated insulin secretion (GSIS) and is a predominant component of the pathophysiology of diabetes. Imeglimin, a novel first-in-class small molecule tetrahydrotriazine drug candidate, improves glycemia and GSIS in preclinical models and clinical trials in patients with Type 2 diabetes; however, the mechanism by which it restores β-cell function is unknown. Here, we show that imeglimin acutely and directly amplifies GSIS in islets isolated from rodents with Type 2 diabetes via a mode of action that is distinct from other known therapeutic approaches. Read More

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February 2021

Promoting Pro-Endocrine Differentiation and Graft Maturation Following Surgical Resection of the Mouse Pancreas.

Methods Mol Biol 2021 ;2224:87-98

Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.

Type 1 diabetes (T1D) is an autoimmune disease, where insulin-producing β-cells in the pancreas are inappropriately recognized and destroyed by immune cells. Islet transplantation is the most successful cell-based therapy for T1D individuals who experience frequent and severe life-threatening hypoglycemia. However, this therapy is extremely restricted owing to the limited availability of donor pancreas. Read More

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Intestinal fatty acid-binding protein, a biomarker of intestinal barrier dysfunction, increases with the progression of type 2 diabetes.

PeerJ 2021 2;9:e10800. Epub 2021 Feb 2.

Department of Critical Care Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.

Objective: To investigate serum intestinal fatty acid-binding protein (I-FABP) in two groups of patients with different duration of hyperglycemia in a cross-sectional study.

Materials And Methods: In the present study, a total of 280 individuals (158 outpatients and 122 inpatients) suffering from hyperglycemia were recruited between May and September 2019. The clinical information of all participants was collected from the hospital information system, including the duration of hyperglycemia, age, gender, hemoglobin A1c (HbA1c), 75-g oral glucose tolerance test including fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting C-peptide (FC-pep), 2-hour C-peptide (2hC-pep), fasting insulin (FIns), and 2-hour insulin (2hIns). Read More

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February 2021

Synthesis of Yakuchinone B-Inspired Inhibitors against Islet Amyloid Polypeptide Aggregation.

J Nat Prod 2021 Feb 18. Epub 2021 Feb 18.

Ph D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei 110, Taiwan.

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction and insulin resistance. Islet amyloid polypeptide (IAPP) aggregation is found to induce islet β-cell death in T2DM patients. Recently, we demonstrated that yakuchinone B derivative exhibited inhibitory activity against IAPP aggregation. Read More

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February 2021

Developmental exposures to perfluorooctanesulfonic acid (PFOS) impact embryonic nutrition, pancreatic morphology, and adiposity in the zebrafish, Danio rerio.

Environ Pollut 2021 Apr 4;275:116644. Epub 2021 Feb 4.

Department of Environmental Health Sciences, University of Massachusetts School of Public Health and Health Sciences, Amherst, MA, 01003, USA.

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant previously found in consumer surfactants and industrial fire-fighting foams. PFOS has been widely implicated in metabolic dysfunction across the lifespan, including diabetes and obesity. However, the contributions of the embryonic environment to metabolic disease remain uncharacterized. Read More

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TGF-β Signaling in Pancreatic Islet β Cell Development and Function.

Endocrinology 2021 Mar;162(3)

Cell Growth and Metabolism Section, Diabetes, Endocrinology & Obesity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Clinical Research Center, Bethesda, MD, USA.

Pancreatic islet beta cells (β-cells) synthesize and secrete insulin in response to rising glucose levels and thus are a prime target in both major forms of diabetes. Type 1 diabetes ensues due to autoimmune destruction of β-cells. On the other hand, the prevailing insulin resistance and hyperglycemia in type 2 diabetes (T2D) elicits a compensatory response from β-cells that involves increases in β-cell mass and function. Read More

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