The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity.

Abstract:

:It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a "perfect storm" critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes.

journal_name

Diabetes

journal_title

Diabetes

authors

Vaarala O,Atkinson MA,Neu J

doi

10.2337/db08-0331

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

2555-62

issue

10

eissn

0012-1797

issn

1939-327X

pii

57/10/2555

journal_volume

57

pub_type

杂志文章,评审

相关文献

DIABETES文献大全
  • A Primary Role for α-Cells as Amino Acid Sensors.

    abstract::Glucagon and its partner insulin are dually linked in both their secretion from islet cells and their action in the liver. Glucagon signaling increases hepatic glucose output, and hyperglucagonemia is partly responsible for the hyperglycemia in diabetes, making glucagon an attractive target for therapeutic interventio...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/dbi19-0021

    authors: Dean ED

    更新日期:2020-04-01 00:00:00

  • A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11.

    abstract::Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sha...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.3.675

    authors: Parker A,Meyer J,Lewitzky S,Rennich JS,Chan G,Thomas JD,Orho-Melander M,Lehtovirta M,Forsblom C,Hyrkkö A,Carlsson M,Lindgren C,Groop LC

    更新日期:2001-03-01 00:00:00

  • Female rats do not exhibit free fatty acid-induced insulin resistance.

    abstract::It is well described that excessive lipid metabolism can cause insulin resistance in both animals and humans, and this has been implicated as a causative factor in the development of insulin resistance and type 2 diabetes in humans. Recently, we have shown that intravenous lipid emulsion (liposyn) infusion during a 12...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.6.1907

    authors: Hevener A,Reichart D,Janez A,Olefsky J

    更新日期:2002-06-01 00:00:00

  • New monoclonal antibody diagnostic reagents for type I diabetes: differential lymphocyte surface antigen expression related to disease.

    abstract::New cellular-based reagents are needed to diagnose type I diabetes as well as to monitor the outcomes of clinical trials at early time points. Four new monoclonal antibodies (mAbs) have been shown to demonstrate reduced binding to lymphocytes from identical twins with long-term type I diabetes relative to that observe...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.3.363

    authors: Pinies JA,Fu Y,Vazquez JA,Faustman D

    更新日期:1997-03-01 00:00:00

  • Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic beta-cells against oxidative stress.

    abstract::Current evidence suggests that reactive oxygen species (ROS) may participate in the destruction of pancreatic beta-cells leading to type 1 diabetes. Genetic factors pre-disposing individual susceptibility to type 1 diabetes might therefore include those affecting the efficacy of ROS metabolism. In a direct in vivo tes...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.46.10.1563

    authors: Kubisch HM,Wang J,Bray TM,Phillips JP

    更新日期:1997-10-01 00:00:00

  • Improvement in β-cell secretory capacity after human islet transplantation according to the CIT07 protocol.

    abstract::The Clinical Islet Transplantation 07 (CIT07) protocol uses antithymocyte globulin and etanercept induction, islet culture, heparinization, and intensive insulin therapy with the same low-dose tacrolimus and sirolimus maintenance immunosuppression as in the Edmonton protocol. To determine whether CIT07 improves engraf...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-1802

    authors: Rickels MR,Liu C,Shlansky-Goldberg RD,Soleimanpour SA,Vivek K,Kamoun M,Min Z,Markmann E,Palangian M,Dalton-Bakes C,Fuller C,Chiou AJ,Barker CF,Luning Prak ET,Naji A

    更新日期:2013-08-01 00:00:00

  • Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reduced beta-cell mass.

    abstract:OBJECTIVE:C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about beta-cell failure in these mice. RESEARCH DESIGN AND METHODS:DIO mice were separated in two groups according to body weig...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1452

    authors: Peyot ML,Pepin E,Lamontagne J,Latour MG,Zarrouki B,Lussier R,Pineda M,Jetton TL,Madiraju SR,Joly E,Prentki M

    更新日期:2010-09-01 00:00:00

  • Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice.

    abstract:OBJECTIVE:In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood ("hypertriglyceridemia") represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceri...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db08-1184

    authors: Narvekar P,Berriel Diaz M,Krones-Herzig A,Hardeland U,Strzoda D,Stöhr S,Frohme M,Herzig S

    更新日期:2009-05-01 00:00:00

  • Increasing GLP-1-induced beta-cell proliferation by silencing the negative regulators of signaling cAMP response element modulator-alpha and DUSP14.

    abstract:OBJECTIVE:Glucagon-like peptide-1 (GLP-1) is a growth and differentiation factor for mature beta-cells and their precursors. However, the overall effect of GLP-1 on increasing beta-cell mass in both in vivo and in vitro conditions is relatively small, and augmenting this effect would be beneficial for the treatment or ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-1414

    authors: Klinger S,Poussin C,Debril MB,Dolci W,Halban PA,Thorens B

    更新日期:2008-03-01 00:00:00

  • Cdkn2a/p16Ink4a regulates fasting-induced hepatic gluconeogenesis through the PKA-CREB-PGC1α pathway.

    abstract::Type 2 diabetes (T2D) is hallmarked by insulin resistance, impaired insulin secretion, and increased hepatic glucose production. The worldwide increasing prevalence of T2D calls for efforts to understand its pathogenesis in order to improve disease prevention and management. Recent genome-wide association studies have...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1921

    authors: Bantubungi K,Hannou SA,Caron-Houde S,Vallez E,Baron M,Lucas A,Bouchaert E,Paumelle R,Tailleux A,Staels B

    更新日期:2014-10-01 00:00:00

  • Metabolic endotoxemia initiates obesity and insulin resistance.

    abstract::Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endoto...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1491

    authors: Cani PD,Amar J,Iglesias MA,Poggi M,Knauf C,Bastelica D,Neyrinck AM,Fava F,Tuohy KM,Chabo C,Waget A,Delmée E,Cousin B,Sulpice T,Chamontin B,Ferrières J,Tanti JF,Gibson GR,Casteilla L,Delzenne NM,Alessi MC,Burceli

    更新日期:2007-07-01 00:00:00

  • Development and function of diabetogenic T-cells in B-cell-deficient nonobese diabetic mice.

    abstract::Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.763

    authors: Chiu PP,Serreze DV,Danska JS

    更新日期:2001-04-01 00:00:00

  • A new murine model of islet xenograft rejection: graft destruction is dependent on a major histocompatibility-specific interaction between T-cells and macrophages.

    abstract::A new murine model of porcine islet-like cell cluster (ICC) xenograft rejection, avoiding interference of unspecific inflammation, was introduced and used to investigate rejection mechanisms. Athymic (nu/nu) mice were transplanted with syngeneic, allogeneic, or xenogeneic islets under the kidney capsule. After the ori...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.5.1111

    authors: Schmidt P,Krook H,Maeda A,Korsgren O,Benda B

    更新日期:2003-05-01 00:00:00

  • Effects of insulin and IGF-I on vascular smooth muscle glucose and cation metabolism.

    abstract::Data is accumulating indicating that impaired insulin action predisposes to increased vascular smooth muscle (VSM) tone, the hallmark of hypertension associated with diabetes. During the last several years, it has been established that VSM is an insulin-sensitive tissue like skeletal muscle and adipocytes. Investigato...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.45.3.s47

    authors: Sowers JR

    更新日期:1996-07-01 00:00:00

  • Manganese-mediated MRI signals correlate with functional β-cell mass during diabetes progression.

    abstract::Diabetes diagnostic therapy and research would strongly benefit from noninvasive accurate imaging of the functional β-cells in the pancreas. Here, we developed an analysis of functional β-cell mass (BCM) by measuring manganese (Mn(2+)) uptake kinetics into glucose-stimulated β-cells by T1-weighted in vivo Mn(2+)-media...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-0864

    authors: Meyer A,Stolz K,Dreher W,Bergemann J,Holebasavanahalli Thimmashetty V,Lueschen N,Azizi Z,Khobragade V,Maedler K,Kuestermann E

    更新日期:2015-06-01 00:00:00

  • Aberrant expression of HLA-DR antigens by insulin-containing beta-cells in recent-onset type I diabetes mellitus.

    abstract::The pancreases of 14 children who died of type I diabetes were studied immunohistochemically for aberrant expression of HLA-DR antigens on islet endocrine cells. Two cases in which no residual insulin-secreting beta-cells were present had no evidence of HLA-DR expression on endocrine cells. Insulin-containing islets w...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.11.1215

    authors: Foulis AK,Farquharson MA

    更新日期:1986-11-01 00:00:00

  • Genetic background determines the size and structure of the endocrine pancreas.

    abstract::Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.1.133

    authors: Bock T,Pakkenberg B,Buschard K

    更新日期:2005-01-01 00:00:00

  • Biohybrid artificial pancreas. Long-term insulin secretion by devices seeded with canine islets.

    abstract::Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture med...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.9.850

    authors: Araki Y,Solomon BA,Basile RM,Chick WL

    更新日期:1985-09-01 00:00:00

  • Potential role of bradykinin in forearm muscle metabolism in humans.

    abstract::Using the euglycemic-hyperinsulinemic glucose clamp and the human forearm technique, we have demonstrated that the improved glucose disposal rate observed after the administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril may be primarily due to increased muscle glucose uptake (MGU). These ...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.45.1.s110

    authors: Dietze GJ,Wicklmayr M,Rett K,Jacob S,Henriksen EJ

    更新日期:1996-01-01 00:00:00

  • Invariant natural killer T-cell control of type 1 diabetes: a dendritic cell genetic decision of a silver bullet or Russian roulette.

    abstract:OBJECTIVE:In part, activation of invariant natural killer T (iNKT)-cells with the superagonist alpha-galactosylceramide (alpha-GalCer) inhibits the development of T-cell-mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotol...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1116

    authors: Driver JP,Scheuplein F,Chen YG,Grier AE,Wilson SB,Serreze DV

    更新日期:2010-02-01 00:00:00

  • Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

    abstract::Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed interv...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1390

    authors: Maessen DE,Brouwers O,Gaens KH,Wouters K,Cleutjens JP,Janssen BJ,Miyata T,Stehouwer CD,Schalkwijk CG

    更新日期:2016-04-01 00:00:00

  • Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model.

    abstract::Diabetic nephropathy is one of the major microvascular complications in diabetes and is the leading cause of end-stage renal disease worldwide. Among various factors, angiogenesis-associated factors such as vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-2 are involved in the development of diabetic...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.10.2891

    authors: Ichinose K,Maeshima Y,Yamamoto Y,Kitayama H,Takazawa Y,Hirokoshi K,Sugiyama H,Yamasaki Y,Eguchi K,Makino H

    更新日期:2005-10-01 00:00:00

  • Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model.

    abstract::Type 1 diabetes is preceded by islet β-cell dysfunction, but the mechanisms leading to β-cell dysfunction have not been rigorously studied. Because immune cell infiltration occurs prior to overt diabetes, we hypothesized that activation of inflammatory cascades and appearance of endoplasmic reticulum (ER) stress in β-...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1293

    authors: Tersey SA,Nishiki Y,Templin AT,Cabrera SM,Stull ND,Colvin SC,Evans-Molina C,Rickus JL,Maier B,Mirmira RG

    更新日期:2012-04-01 00:00:00

  • Decreased IRS2 and TIMP3 expression in monocytes from offspring of type 2 diabetic patients is correlated with insulin resistance and increased intima-media thickness.

    abstract:OBJECTIVE:In humans, it is unclear if insulin resistance at the monocyte level is associated with atherosclerosis in vivo. Here we have studied first-degree relatives of patients with type 2 diabetes to investigate whether a reduction in components of the insulin signal transduction pathways, such as the insulin recept...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0162

    authors: Cardellini M,Menghini R,Luzi A,Davato F,Cardolini I,D'Alfonso R,Gentileschi P,Rizza S,Marini MA,Porzio O,Lauro D,Sbraccia P,Lauro R,Federici M

    更新日期:2011-12-01 00:00:00

  • Fractalkine is a novel human adipochemokine associated with type 2 diabetes.

    abstract:OBJECTIVE:Leukocyte infiltration of adipose is a critical determinant of obesity-related metabolic diseases. Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in atherosclerosis, but its role in adipose inflammation and type 2 diabetes is unknown. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0956

    authors: Shah R,Hinkle CC,Ferguson JF,Mehta NN,Li M,Qu L,Lu Y,Putt ME,Ahima RS,Reilly MP

    更新日期:2011-05-01 00:00:00

  • Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.

    abstract:OBJECTIVE:A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 an...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-0506

    authors: Zhao J,Li M,Bradfield JP,Wang K,Zhang H,Sleiman P,Kim CE,Annaiah K,Glaberson W,Glessner JT,Otieno FG,Thomas KA,Garris M,Hou C,Frackelton EC,Chiavacci RM,Berkowitz RI,Hakonarson H,Grant SF

    更新日期:2009-10-01 00:00:00

  • Compensation in pancreatic beta-cell function in subjects with glucokinase mutations.

    abstract::The relationship between the in vivo insulin secretory responsiveness of the pancreatic beta-cell to glucose and the flux of glucose through the enzyme glucokinase was investigated in six subjects with heterozygous glucokinase mutations and in six matched control subjects. This was done by combining data published pre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.5.718

    authors: Sturis J,Kurland IJ,Byrne MM,Mosekilde E,Froguel P,Pilkis SJ,Bell GI,Polonsky KS

    更新日期:1994-05-01 00:00:00

  • Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.

    abstract::Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involve...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.2.227

    authors: Shintani M,Ogawa Y,Ebihara K,Aizawa-Abe M,Miyanaga F,Takaya K,Hayashi T,Inoue G,Hosoda K,Kojima M,Kangawa K,Nakao K

    更新日期:2001-02-01 00:00:00

  • Metabolic studies in the pyelonephritic rat.

    abstract::Insulin antagonism characterizes infection, but the mechanism is unknown. Previous studies have been performed during the acute catabolic stage of infection, and the resultant metabolic changes reflect this decreased food intake and weight loss. To delineate metabolic alterations due to infection itself, rats with pye...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.10.881

    authors: Davidson MB

    更新日期:1975-10-01 00:00:00

  • WISP1 is a novel adipokine linked to inflammation in obesity.

    abstract::WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix-associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade ...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章

    doi:10.2337/db14-0444

    authors: Murahovschi V,Pivovarova O,Ilkavets I,Dmitrieva RM,Döcke S,Keyhani-Nejad F,Gögebakan Ö,Osterhoff M,Kemper M,Hornemann S,Markova M,Klöting N,Stockmann M,Weickert MO,Lamounier-Zepter V,Neuhaus P,Konradi A,Dooley S,von L

    更新日期:2015-03-01 00:00:00