New Understanding of β-Cell Heterogeneity and In Situ Islet Function.

Abstract:

:Insulin-secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific subpopulations with distinct functional characteristics, developmental programs, abilities to proliferate in response to metabolic or developmental cues, and resistance to immune-mediated damage. Importantly, these subpopulations change in disease or aging, including in human disease. Although discovering new β-cell subpopulations has substantially advanced our understanding of islet biology, a point of caution is that these characteristics have often necessarily been identified in single β-cells dissociated from the islet. β-Cells in the islet show extensive communication with each other via gap junctions and with other cell types via diffusible chemical messengers. As such, how these different subpopulations contribute to in situ islet function, including during plasticity, is not well understood. We will discuss recent findings revealing functional β-cell subpopulations in the intact islet, the underlying basis for these identified subpopulations, and how these subpopulations may influence in situ islet function. Furthermore, we will discuss the outlook for emerging technologies to gain further insight into the role of subpopulations in in situ islet function.

journal_name

Diabetes

journal_title

Diabetes

authors

Benninger RKP,Hodson DJ

doi

10.2337/dbi17-0040

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

537-547

issue

4

eissn

0012-1797

issn

1939-327X

pii

67/4/537

journal_volume

67

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Islet cell DNA is a target of inflammatory attack by nitric oxide.

    abstract::NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks....

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.3.496

    authors: Fehsel K,Jalowy A,Qi S,Burkart V,Hartmann B,Kolb H

    更新日期:1993-03-01 00:00:00

  • Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport.

    abstract::We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.10.1217

    authors: Sinha MK,Buchanan C,Leggett N,Martin L,Khazanie PG,Dimarchi R,Pories WJ,Caro JF

    更新日期:1989-10-01 00:00:00

  • Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice.

    abstract::Because polyphenols may have beneficial effects on dyslipidemia, which accelerates atherosclerosis in diabetes, we examined the effect of polyphenols on hepatocellular AMP-activated protein kinase (AMPK) activity and lipid levels, as well as hyperlipidemia and atherogenesis in type 1 diabetic LDL receptor-deficient mi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-1188

    authors: Zang M,Xu S,Maitland-Toolan KA,Zuccollo A,Hou X,Jiang B,Wierzbicki M,Verbeuren TJ,Cohen RA

    更新日期:2006-08-01 00:00:00

  • Functional variants in MBL2 are associated with type 2 diabetes and pre-diabetes traits in Pima Indians and the old order Amish.

    abstract:OBJECTIVE:MBL2 encodes the mannose-binding lectin, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1593

    authors: Muller YL,Hanson RL,Bian L,Mack J,Shi X,Pakyz R,Shuldiner AR,Knowler WC,Bogardus C,Baier LJ

    更新日期:2010-08-01 00:00:00

  • The size of the loading dose as an important determinant of the results of the oral glucose tolerance test: a study in subjects with slightly impaired glucose tolerance.

    abstract::In the oral glucose tolerance test (OGTT), divergent doses of glucose remain in use by virtue of the prevailing conviction that the size of the loading dose hardly affects the outcome of the test. We compared the results of OGTTs with 100-gm. and 50-gm. loads in 85 patients, who were selected for slightly impaired glu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.27.1.42

    authors: de Nobel E,van't Laar A

    更新日期:1978-01-01 00:00:00

  • Failure of genetically selected miniature swine to model NIDDM.

    abstract::Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.3.284

    authors: Hand MS,Surwit RS,Rodin J,Van Order P,Feinglos MN

    更新日期:1987-03-01 00:00:00

  • LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation.

    abstract::Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo sub...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.45.6.762

    authors: Jenkins AJ,Klein RL,Chassereau CN,Hermayer KL,Lopes-Virella MF

    更新日期:1996-06-01 00:00:00

  • Synaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells.

    abstract::Synaptotagmin (Syt)-7, a major component of the exocytotic machinery in neurons, is also the major Syt in rodent pancreatic β-cells shown to mediate glucose-stimulated insulin secretion (GSIS). However, Syt-7's precise exocytotic actions in β-cells remain unknown. We show that Syt-7 is abundant in human β-cells. Adeno...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1436

    authors: Dolai S,Xie L,Zhu D,Liang T,Qin T,Xie H,Kang Y,Chapman ER,Gaisano HY

    更新日期:2016-07-01 00:00:00

  • Human pancreatic β-cell G1/S molecule cell cycle atlas.

    abstract::Expansion of pancreatic β-cells is a key goal of diabetes research, yet induction of adult human β-cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human β-cell. Here, we provide a comprehensive immunocytochemical "atlas" of G1/S control m...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0777

    authors: Fiaschi-Taesch NM,Kleinberger JW,Salim FG,Troxell R,Wills R,Tanwir M,Casinelli G,Cox AE,Takane KK,Scott DK,Stewart AF

    更新日期:2013-07-01 00:00:00

  • Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine β-Cells.

    abstract::Transcription factor expression fluctuates during β-cell ontogeny, and disruptions in this pattern can affect the development or function of those cells. Here we uncovered that murine endocrine pancreatic progenitors express high levels of the homeodomain transcription factor Prox1, whereas both immature and mature β-...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0713

    authors: Paul L,Walker EM,Drosos Y,Cyphert HA,Neale G,Stein R,South J,Grosveld G,Herrera PL,Sosa-Pineda B

    更新日期:2016-03-01 00:00:00

  • Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: II. Immunologic analysis.

    abstract::Recently, we identified in normally type 1 diabetes-prone NOD/LtJ mice a spontaneous new leptin receptor (LEPR) mutation (designated Lepr(db-5J)) producing juvenile obesity, hyperglycemia, hyperinsulinemia, and hyperleptinemia. This early type 2 diabetes syndrome suppressed intra-islet insulitis and permitted spontane...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:

    authors: Lee CH,Chen YG,Chen J,Reifsnyder PC,Serreze DV,Clare-Salzler M,Rodriguez M,Wasserfall C,Atkinson MA,Leiter EH

    更新日期:2006-01-01 00:00:00

  • Mannose phosphorylation by glucokinase from liver and transplantable insulinoma. Cooperativity and discrimination of anomers.

    abstract::Glucokinase from rat liver or transplantable, radiation-induced insulinomas was partially purified by ion exchange chromatography using DEAE-Cibacron Blue F3GA agarose. Phosphorylation of alpha,beta-D-mannose by glucokinase occurred with cooperative rate dependence on mannose concentration (nH: 1.50). Half-maximal pho...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.12.1146

    authors: Meglasson MD,Schinco M,Matschinsky FM

    更新日期:1983-12-01 00:00:00

  • Rapid increase in circulating leptin in ventromedial hypothalamus-lesioned rats: role of hyperinsulinemia and implication for upregulation mechanism.

    abstract::The mechanisms of marked increase in plasma leptin soon after ventromedial hypothalamus (VMH) lesions were investigated. Although rats did not gain body weight or parametrial fat-pad mass 24 h after the operation, the acute VMH-lesioned rats exhibited substantial five- and fourfold increases in plasma leptin levels co...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.10.2034

    authors: Suga A,Hirano T,Kageyama H,Kashiba M,Oka J,Osaka T,Namba Y,Tsuji M,Miura M,Adachi M,Inoue S

    更新日期:1999-10-01 00:00:00

  • Two-color flow cytometry analysis of activated T-lymphocyte subsets in type I diabetes mellitus.

    abstract::We addressed the question of whether newly diagnosed type I (insulin-dependent) diabetes mellitus patients showed an increased number of DR (la+) T-lymphocytes compared with nondiabetic siblings and normal control subjects. Two-color flow cytometry measurements of peripheral-blood lymphocytes showed a slight but stati...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.6.792

    authors: Legendre CM,Schiffrin A,Weitzner G,Colle E,Guttmann RD

    更新日期:1988-06-01 00:00:00

  • Long-term metabolic control by rat islet grafts depends on the composition of the implant.

    abstract::This study examines whether the loss of metabolic control in initially normalized islet transplants can result from the inadequate composition of the donor tissue. Streptozotocin-induced diabetic rats were followed for 64 weeks after the intraportal injection of islet isografts with different composition. The implanta...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.45.12.1814

    authors: Keymeulen B,Korbutt G,De Paepe M,Gorus F,Klöppel G,Pipeleers DG

    更新日期:1996-12-01 00:00:00

  • Platelet aggregation in experimental diabetes and experimental galactosemia.

    abstract::Platelet aggregation and related plasma factors have been studied in experimentally diabetic dogs, experimentally galactosemic dogs, and in normal dogs. Platelet aggregation, when induced in vitro by ADP (up to 22 microM) or collagen (up to 4 micrograms/ml), was not significantly different from normal in the diabetic ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.9.846

    authors: Kern TS,Engerman RL

    更新日期:1984-09-01 00:00:00

  • Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.

    abstract::Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The object...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.3.508

    authors: Hansen L,Echwald SM,Hansen T,Urhammer SA,Clausen JO,Pedersen O

    更新日期:1997-03-01 00:00:00

  • Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas.

    abstract::The transcription factor regulatory factor X (RFX)-3 regulates the expression of genes required for the growth and function of cilia. We show here that mouse RFX3 is expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults. RFX3 expression already is evident in early Ngn3-positi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1187

    authors: Ait-Lounis A,Baas D,Barras E,Benadiba C,Charollais A,Nlend Nlend R,Liègeois D,Meda P,Durand B,Reith W

    更新日期:2007-04-01 00:00:00

  • Tetracycline treatment retards the onset and slows the progression of diabetes in human amylin/islet amyloid polypeptide transgenic mice.

    abstract:OBJECTIVE:Aggregation of human amylin/islet amyloid polypeptide (hA/hIAPP) into small soluble beta-sheet-containing oligomers is linked to islet beta-cell degeneration and the pathogenesis of type 2 diabetes. Here, we used tetracycline, which modifies hA/hIAPP oligomerization, to probe mechanisms whereby hA/hIAPP cause...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0548

    authors: Aitken JF,Loomes KM,Scott DW,Reddy S,Phillips AR,Prijic G,Fernando C,Zhang S,Broadhurst R,L'Huillier P,Cooper GJ

    更新日期:2010-01-01 00:00:00

  • Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes.

    abstract::Hepatocyte nuclear factor 4alpha (HNF4A), the gene for the maturity-onset diabetes of the young type 1 monogenic form of type 2 diabetes, is within the type 2 diabetes-linked region on chromosome 20q12-q13.1 and, consequently, is a positional candidate gene for type 2 diabetes in the general population. Previous studi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.4.1185

    authors: Bagwell AM,Bento JL,Mychaleckyj JC,Freedman BI,Langefeld CD,Bowden DW

    更新日期:2005-04-01 00:00:00

  • Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats.

    abstract::Zucker (fa/fa) rats with defective leptin receptors are obese, hyperphagic, and hyperinsulinemic. For testing whether chronic activation of the central melanocortin pathway can bypass the defective leptin signaling and normalize altered energy homeostasis in these rats, recombinant adeno-associated virus encoding pro-...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.8.1951

    authors: Li G,Mobbs CV,Scarpace PJ

    更新日期:2003-08-01 00:00:00

  • Elevated mRNA levels of major histocompatibility complex class II genes in lymphocytes of autoimmune BB rats.

    abstract::The BB rat spontaneously develops autoimmune abnormalities such as insulin-dependent diabetes mellitus and thyroiditis. The autoimmunity of the BB rat is controlled in part by genes of the major histocompatibility complex (MHC), known as the RT1 complex in the rat, and accumulating evidence suggests the involvement of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.12.1637

    authors: Holowachuk EW,Greer MK,Martin DR

    更新日期:1988-12-01 00:00:00

  • Heterogeneity of the Human Pancreatic Islet.

    abstract::Pancreatic β-cells play a pivotal role in maintaining normoglycemia. Recent studies have revealed that the β-cell is not a homogeneous cell population but, rather, is heterogeneous in a number of properties such as electrical activity, gene expression, and cell surface markers. Identification of specific β-cell subpop...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0072

    authors: Dybala MP,Hara M

    更新日期:2019-06-01 00:00:00

  • Fat-Specific Sirt6 Ablation Sensitizes Mice to High-Fat Diet-Induced Obesity and Insulin Resistance by Inhibiting Lipolysis.

    abstract::Sirt6 is an NAD+-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. In this study, we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet-induced obesity, which was attributed to ad...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1225

    authors: Kuang J,Zhang Y,Liu Q,Shen J,Pu S,Cheng S,Chen L,Li H,Wu T,Li R,Li Y,Zou M,Zhang Z,Jiang W,Xu G,Qu A,Xie W,He J

    更新日期:2017-05-01 00:00:00

  • A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells.

    abstract::The incretin hormones, glucagon-like peptide 1 and pituitary adenylyl cyclase-activating polypeptide, are proposed to activate a maitotoxin (MTX)-sensitive, Ca2+-dependent nonselective cation current in pancreatic beta-cells and insulinoma cells. This MTX-sensitive current is present in human beta-cells as well as in ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.7.1066

    authors: Leech CA,Habener JF

    更新日期:1998-07-01 00:00:00

  • Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes.

    abstract::β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the rol...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0022

    authors: Jørgensen NB,Dirksen C,Bojsen-Møller KN,Jacobsen SH,Worm D,Hansen DL,Kristiansen VB,Naver L,Madsbad S,Holst JJ

    更新日期:2013-09-01 00:00:00

  • Diabetic patients without vascular complications display enhanced basal platelet activation and decreased antioxidant status.

    abstract::Vascular complications are the leading causes of morbidity and mortality in diabetic patients. The contribution of platelets to thromboembolic complications is well documented, but their involvement in the initiation of the atherosclerotic process is of rising interest. Thus, the aim of the present study was to evalua...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.4.1046

    authors: Véricel E,Januel C,Carreras M,Moulin P,Lagarde M

    更新日期:2004-04-01 00:00:00

  • Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo.

    abstract:OBJECTIVE:Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose tr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0120

    authors: Chari M,Yang CS,Lam CK,Lee K,Mighiu P,Kokorovic A,Cheung GW,Lai TY,Wang PY,Lam TK

    更新日期:2011-07-01 00:00:00

  • Intranasal insulin ameliorates experimental diabetic neuropathy.

    abstract:OBJECTIVE:We hypothesized that intranasal insulin (I-I) delivery targets the nervous system while avoiding potential adverse systemic effects when compared with subcutaneous insulin (S-I) for experimental streptozotocin-induced diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS:I-I or S-I at 0.87 IU dai...

    journal_title:Diabetes

    pub_type: 杂志文章,收录出版

    doi:10.2337/db08-1287

    authors: Francis G,Martinez J,Liu W,Nguyen T,Ayer A,Fine J,Zochodne D,Hanson LR,Frey WH 2nd,Toth C

    更新日期:2009-04-01 00:00:00

  • Nutrient excess stimulates β-cell neogenesis in zebrafish.

    abstract::Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1841

    authors: Maddison LA,Chen W

    更新日期:2012-10-01 00:00:00