Article PubMed Protecting against neurodegenerative diseases Central Google Scholar Bergman, R. This Pxncreatic also meant a gradual return to proper beta cell function and mass. Contacts Sophie Kluthe C: sophie.

Pancreatic beta cells -

Oram, R. Beta cells in type 1 diabetes: mass and function; sleeping or dead? Thompson, P. Targeted elimination of senescent beta cells prevents type 1 diabetes. e10 Damond, N. A map of human type 1 diabetes progression by imaging mass cytometry.

e5 Strandell, E. Reversal of beta-cell suppression in vitro in pancreatic islets isolated from nonobese diabetic mice during the phase preceding insulin-dependent diabetes mellitus.

Function of isolated pancreatic islets from patients at onset of type 1 diabetes: insulin secretion can be restored after some days in a nondiabetogenic environment in vitro: results from the DiViD study. Diabetes 64 , — Marchetti, P. Function of pancreatic islets isolated from a type 1 diabetic patient.

Diabetes Care 23 , — Brissova, M. α cell function and gene expression are compromised in type 1 diabetes. Cell Rep. Mastracci, T. Distinct gene expression pathways in islets from individuals with short- and long-duration type 1 diabetes.

Marroqui, L. Pancreatic α cells are resistant to metabolic stress-induced apoptosis in type 2 diabetes. EBioMedicine 2 , — Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells.

eLife 4 , e Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors. This study provides one of the first solid pieces of evidence that some pancreatic β-cells may survive and secrete insulin many years after onset of T1DM.

Proinsulin secretion is a persistent feature of type 1 diabetes. Relevant evidence that surviving β-cells in T1DM may be able to synthesize proinsulin but fail to process it into mature insulin.

Lam, C. Low-level insulin content within abundant non-β islet endocrine cells in long-standing type 1 diabetes. Thorel, F. Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature , — Courtney, M. The inactivation of Arx in pancreatic α-cells triggers their neogenesis and conversion into functional β-like cells.

PLoS Genet. Can GABA turn pancreatic α-cells into β-cells? Ortis, F. Cytokines interleukin-1β and tumor necrosis factor-α regulate different transcriptional and alternative splicing networks in primary β-cells. Diabetes 59 , — The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines.

Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes.

Diabetologia 60 , — Osum, K. Interferon-gamma drives programmed death-ligand 1 expression on islet β cells to limit T cell function during autoimmune diabetes. Wyatt, R. What the HLA-I! Classical and non-classical HLA class I and their potential roles in type 1 diabetes.

Akturk, H. Immune checkpoint inhibitor-induced type 1 diabetes: a systematic review and meta-analysis. Moore, F. STAT1 is a master regulator of pancreatic β-cell apoptosis and islet inflammation. Lundberg, M. Expression of interferon-stimulated genes in insulitic pancreatic islets of patients recently diagnosed with type 1 diabetes.

Diabetes 65 , — Ramos-Rodriguez, M. The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes. This study identifies, for the first time, β-cell stimulus-responsive regulatory elements and finds that they are implicated in the genetic risk of T1DM, possibly playing a role in the early stages of the disease.

Russell, M. HLA class II antigen processing and presentation pathway components demonstrated by transcriptome and protein analyses of islet β-cells from donors with type 1 diabetes.

Xin, Y. RNA sequencing of single human islet cells reveals type 2 diabetes genes. Rahier, J. Pancreatic β-cell mass in European subjects with type 2 diabetes. Butler, A. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes.

Diabetes 52 , — Sakuraba, H. Reduced β-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia 45 , 85—96 Hanley, S. β-cell mass dynamics and islet cell plasticity in human type 2 diabetes.

Endocrinology , — Yoon, K. Selective β-cell loss and α-cell expansion in patients with type 2 diabetes mellitus in Korea. Del Guerra, S. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Raleigh, D. The β-cell assassin: IAPP cytotoxicity.

Richardson, S. Islet-associated macrophages in type 2 diabetes. Diabetologia 52 , — Henquin, J. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Diabetologia 54 , — Utzschneider, K.

Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 32 , — Green, D. The clearance of dying cells: table for two. Cell Death Differ. The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation.

Diabetologia 53 , — This study modelled lipofuscin accumulation in human β-cells with age; together with the complementary methods used in reference 84, this shows that, past age 20—30 years, little or no new β-cells are formed and β-cells age with the body.

Longevity of human islet α- and β-cells. Perl, S. Significant human β-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating. Gregg, B. Formation of a human β-cell population within pancreatic islets is set early in life.

β-cell deficit in obese type 2 diabetes, a minor role of β-cell dedifferentiation and degranulation. Md Moin, A. Increased frequency of hormone negative and polyhormonal endocrine cells in lean individuals with type 2 diabetes.

Cinti, F. Evidence of β-cell dedifferentiation in human type 2 diabetes. Sun, J. PubMed Google Scholar. Spijker, H. Loss of β-cell identity occurs in type 2 diabetes and is associated with islet amyloid deposits.

Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors.

Diabetes 62 , — Masini, M. Co-localization of acinar markers and insulin in pancreatic cells of subjects with type 2 diabetes. PLoS One 12 , e Tamura, Y. Telomere attrition in beta and alpha cells with age. Age 38 , 61 β-cell telomere attrition in diabetes: inverse correlation between HbA1c and telomere length.

Aguayo-Mazzucato, C. Acceleration of β cell aging determines diabetes and senolysis improves disease outcomes. e4 Gunton, J. Cell , — Solimena, M. Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.

Fadista, J. Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Natl Acad. USA , — Marselli, L. Gene expression profiles of beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes.

PLoS One 5 , e Wang, Y. Single-cell RNA-seq of the pancreatic islets-a promise not yet fulfilled? Carrano, A. Interrogating islets in health and disease with single-cell technologies.

Bosco, D. Actively synthesizing β-cells secrete preferentially after glucose stimulation. Pipeleers, D. Heterogeneity in pancreatic β-cell population. Diabetes 41 , — Salomon, D. Heterogeneity and contact-dependent regulation of hormone secretion by individual B cells.

Cell Res. Ling, Z. Intercellular differences in interleukin 1β-induced suppression of insulin synthesis and stimulation of noninsulin protein synthesis by rat pancreatic β-cells. Mawla, A. Navigating the depths and avoiding the shallows of pancreatic islet cell transcriptomes.

An excellent analysis of heterogeneity and caveats of single islet cell RNA sequencing. Mahajan, A. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.

Onengut-Gumuscu, S. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Cudworth, A. Letter: HL-A antigens and diabetes mellitus. Lancet 2 , Polychronakos, C. Understanding type 1 diabetes through genetics: advances and prospects.

Floyel, T. CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients. Koskinen, M. Longitudinal pattern of first-phase insulin response is associated with genetic variants outside the class II HLA region in children with multiple autoantibodies.

Diabetes 69 , 12—19 Maurano, M. Systematic localization of common disease-associated variation in regulatory DNA. Science , — Dupuis, J. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Minton, J. Association studies of genetic variation in the WFS1 gene and type 2 diabetes in U. Diabetes 51 , — Sandhu, M. Common variants in WFS1 confer risk of type 2 diabetes. Cheurfa, N. Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the data from Epidemiological Study on the Insulin Resistance Syndrome DESIR prospective study.

Pennacchio, L. Limits of sequence and functional conservation. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature , 57—74 Bernstein, B. The NIH roadmap epigenomics mapping consortium. Pasquali, L. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants.

This study unravelled that DNA variation at islet enhancers plays a role in the genetic predisposition to T2DM and provides a reference cis -regulatory map for ongoing efforts to dissect the transcriptional program of pancreatic β-cells. Parker, S. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.

Gaulton, K. A map of open chromatin in human pancreatic islets. Bhandare, R. Genome-wide analysis of histone modifications in human pancreatic islets. Genome Res. Fogarty, M. Allele-specific transcriptional activity at type 2 diabetes-associated single nucleotide polymorphisms in regions of pancreatic islet open chromatin at the JAZF1 locus.

Kulzer, J. A common functional regulatory variant at a type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell. Horikoshi, M. Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms. Greenwald, W. Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk.

Miguel-Escalada, I. Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes. This study resolved 3D chromatin contact maps in human islet cells allowing the identification of promoter targets of distal regulatory elements at T2DM and fasting glucose GWAS loci.

Redondo, M. Concordance for islet autoimmunity among monozygotic twins. Aly, T. Extreme genetic risk for type 1A diabetes. Winkler, C. Feature ranking of type 1 diabetes susceptibility genes improves prediction of type 1 diabetes. A type 1 diabetes genetic risk score can aid discrimination between type 1 and type 2 diabetes in young adults.

Diabetes Care 39 , — Bonifacio, E. Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: a prospective study in children. PLoS Med. Sharp, S. Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis.

Le Stunff, C. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Vafiadis, P. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Farh, K.

Genetic and epigenetic fine mapping of causal autoimmune disease variants. Alasoo, K. Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response. Chun, S. Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types.

The role for endoplasmic reticulum stress in diabetes mellitus. Ron, D. Signal integration in the endoplasmic reticulum unfolded protein response. Cell Biol. Endoplasmic reticulum stress and eIF2α phosphorylation: the Achilles heel of pancreatic β cells.

Pirot, P. Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs. Diabetologia 50 , — Tersey, S. Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model.

Diabetes 61 , — Engin, F. Restoration of the unfolded protein response in pancreatic β cells protects mice against type 1 diabetes. Transl Med. Brozzi, F. ER stress and the decline and fall of pancreatic beta cells in type 1 diabetes.

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. Diabetologia 56 , — Morita, S. Targeting ABL-IRE1α signaling spares ER-stressed pancreatic β cells to reverse autoimmune diabetes.

Ghosh, R. Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress. Hagerkvist, R. Amelioration of diabetes by imatinib mesylate Gleevec : role of β-cell NF-κB activation and anti-apoptotic preconditioning. FASEB J. US National Library of Medicine.

Marre, M. β cell ER stress and the implications for immunogenicity in type 1 diabetes. Cell Dev. Kracht, M. Autoimmunity against a defective ribosomal insulin gene product in type 1 diabetes.

Relevant evidence that β-cell stress modifies ribosomal processing of human insulin mRNA-generating neoantigens.

Vomund, A. Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells. USA , E—E Laybutt, D. Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Huang, C. High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated β-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes.

Diabetes 56 , — Hartman, M. Role for activating transcription factor 3 in stress-induced β-cell apoptosis. Hull, R. Amyloid formation in human IAPP transgenic mouse islets and pancreas, and human pancreas, is not associated with endoplasmic reticulum stress.

Aberrant islet unfolded protein response in type 2 diabetes. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Chan, J. Failure of the adaptive unfolded protein response in islets of obese mice is linked with abnormalities in β-cell gene expression and progression to diabetes.

Biden, T. Lipotoxic endoplasmic reticulum stress, β cell failure, and type 2 diabetes mellitus. Elouil, H. Acute nutrient regulation of the unfolded protein response and integrated stress response in cultured rat pancreatic islets.

Lipson, K. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cunha, D. Initiation and execution of lipotoxic ER stress in pancreatic β-cells.

Cell Sci. Death protein 5 and pupregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis. Selective inhibition of eukaryotic translation initiation factor 2α dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic β-cell dysfunction and apoptosis.

Ladrière, L. Enhanced signaling downstream of ribonucleic acid-activated protein kinase-like endoplasmic reticulum kinase potentiates lipotoxic endoplasmic reticulum stress in human islets. Abdulkarim, B. Guanabenz sensitizes pancreatic β cells to lipotoxic endoplasmic reticulum stress and apoptosis.

A missense mutation in PPP1R15B causes a syndrome including diabetes, short stature, and microcephaly. Delepine, M. EIF2AK3, encoding translation initiation factor 2-α kinase 3, is mutated in patients with Wolcott-Rallison syndrome.

De Franco, E. Diabetes 69 , — Synofzik, M. Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration. Skopkova, M. EIF2S3 mutations associated with severe X-linked intellectual disability syndrome MEHMO. Inoue, H. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy Wolfram syndrome.

Valero, R. Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene. Bonnycastle, L. Autosomal dominant diabetes arising from a Wolfram syndrome 1 mutation. Bensellam, M. Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions.

Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms. Diabetologia 58 , — Xiao, C.

Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and β-cell dysfunction in humans. Diabetes 60 , — Plaisier, S.

Rank-rank hypergeometric overlap: identification of statistically significant overlap between gene-expression signatures. Nucleic Acids Res.

Download references. We thank M. Colli, ULB Center for Diabetes Research, for preparing Fig. Ramos-Rodríguez, IGTP, for preparing part of Fig. acknowledges the support of a grant from the Welbio-FNRS Fonds National de la Recherche Scientifique , Belgium, the Dutch Diabetes Fonds DDFR , Holland, and start up-funds from the Indiana Biosciences Research Institute IBRI , Indianapolis, Indiana, USA.

and M. and Harry B. Helmsley Charitable Trust; and the Innovative Medicines Initiative 2 Joint Undertaking Rhapsody, under grant agreement No. acknowledges the support of the FNRS, Belgium. acknowledges the support of grants from the Spanish Ministry of Economy and Competitiveness SAFR , Marató TV3 We preferentially selected publications in the past 5 years, plus earlier key publications for citation.

A manual search of some references cited in these papers or in relevant articles related to the role of pancreatic β-cells in the pathogenesis of diabetes was also done. All selected papers were English-language, full-text articles. Review articles are often cited to provide the readers with additional references.

Many of the references identified could not be included owing to space restrictions. ULB Center for Diabetes Research, Welbio Investigator, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.

Indiana Biosciences Research Institute IBRI , Indianapolis, IN, USA. Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain. Josep Carreras Leukaemia Research Institute, Barcelona, Spain. ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium.

Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium. You can also search for this author in PubMed Google Scholar. Correspondence to Décio L. Eizirik , Lorenzo Pasquali or Miriam Cnop.

Nature Reviews Endocrinology thanks F. Urano, A. Zaldumbide and the other, anonymous, reviewer s for their contribution to the peer review of this work. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Antigens that have not been previously presented or recognized by the immune system. They can be formed as a result in changes in transcription, translation or post-translational events.

Reprints and permissions. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure. Nat Rev Endocrinol 16 , — Download citation. Insulinomas are usually benign , but may be medically significant and even life-threatening due to recurrent and prolonged attacks of hypoglycemia.

Many researchers around the world are investigating the pathogenesis of diabetes and beta-cell failure. Tools used to study beta-cell function are expanding rapidly with technology.

For instance, transcriptomics have allowed researchers to comprehensively analyze gene transcription in beta-cells to look for genes linked to diabetes. Fluorescent dyes bind to calcium and allow in vitro imaging of calcium activity which correlates directly with insulin release.

Diabetes mellitus can be experimentally induced in vivo for research purposes by streptozotocin [34] or alloxan , [35] which are specifically toxic to beta cells. Research has shown that beta cells can be differentiated from human pancreas progenitor cells.

In order to successfully re-create functional insulin producing beta cells, studies have shown that manipulating cell-signal pathways in early stem cell development will lead to those stem cells differentiating into viable beta cells.

Studies have shown that it is possible to regenerate beta cells in vivo in some animal models. Investigation of beta cells following acute onset of Type 1 diabetes has shown little to no proliferation of newly synthesized beta cells, suggesting that human beta cells might not be as versatile as rat beta cells, but there is actually no comparison that can be made here because healthy non-diabetic rats were used to prove that beta cells can proliferate after intentional destruction of beta cells, while diseased type-1 diabetic humans were used in the study which was attempted to use as evidence against beta cells regenerating.

It appears that much work has to be done in the field of regenerating beta cells. An unlimited amount of beta cells produced artificially could potentially provide therapy to many of the patients who are affected by Type 1 diabetes.

Research focused on non insulin dependent diabetes encompasses many areas of interest. Degeneration of the beta cell as diabetes progresses has been a broadly reviewed topic.

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January Is there a need for re-classification? A narrative review". BMC Endocrine Disorders. Bosnian Journal of Basic Medical Sciences. General Hospital Psychiatry. prospective diabetes study

The Protecting against neurodegenerative diseases of Artificial pancreas research takes place in the Pancdeatic beta cells that are geta in the form of islets Pancreatic beta cells Langerhans together with a few other islet cell types Pqncreatic the pancreas organ. The signal for glucose-induced insulin secretion is generated in two pathways in the mitochondrial metabolism of the pancreatic beta cells. These pathways are also known as the triggering pathway and the amplifying pathway. Glucokinase, the low-affinity glucose-phosphorylating enzyme in beta cell glycolysis acts as the signal-generating enzyme in this process. ATP ultimately generated is the crucial second messenger in this process. Thank ceells for visiting Pancreatic beta cells. You Sports psychology techniques Protecting against neurodegenerative diseases a browser version with limited Pancreaitc for Pancreatic beta cells. To obtain the best Football nutrition for match preparation, we recommend you use a more Pancreayic to date browser Pancreati turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus — type 1 diabetes mellitus T1DM and type 2 diabetes mellitus T2DM. Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease.