Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells.

Abstract:

:In nonobese diabetic (NOD) mice, a deficiency in the number and function of invariant natural killer T-cells (iNKT cells) contributes to the onset of type 1 diabetes. The activation of CD1d-restricted iNKT cells by alpha-galactosylceramide (alpha-GalCer) corrects these deficiencies and protects against spontaneous and recurrent type 1 diabetes. Although interleukin (IL)-4 and IL-10 have been implicated in alpha-GalCer-induced protection from type 1 diabetes, a precise role for these cytokines in iNKT cell regulation of susceptibility to type 1 diabetes has not been identified. Here we use NOD.IL-4(-/-) and NOD.IL-10(-/-) knockout mice to further evaluate the roles of IL-4 and IL-10 in alpha-GalCer-induced protection from type 1 diabetes. We found that IL-4 but not IL-10 expression mediates protection against spontaneous type 1 diabetes, recurrent type 1 diabetes, and prolonged syngeneic islet graft function. Increased transforming growth factor-beta gene expression in pancreatic lymph nodes may be involved in alpha-GalCer-mediated protection in NOD.IL-10(-/-) knockout mice. Unlike the requirement of IL-7 and IL-15 to maintain iNKT cell homeostasis, IL-4 and IL-10 are not required for alpha-GalCer-induced iNKT cell expansion and/or survival. Our data identify an important role for IL-4 in the protection against type 1 diabetes by activated iNKT cells, and these findings have important implications for cytokine-based therapy of type 1 diabetes and islet transplantation.

journal_name

Diabetes

journal_title

Diabetes

authors

Mi QS,Ly D,Zucker P,McGarry M,Delovitch TL

doi

10.2337/diabetes.53.5.1303

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

1303-10

issue

5

eissn

0012-1797

issn

1939-327X

journal_volume

53

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Intraislet Ghrelin Signaling Does Not Regulate Insulin Secretion From Adult Mice.

    abstract::Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0079

    authors: Gray SM,Niu J,Zhang A,Svendsen B,Campbell JE,D'Alessio DA,Tong J

    更新日期:2019-09-01 00:00:00

  • New principle for large-scale preparation of purified human pancreas islets.

    abstract::Because successful human islet transplantation requires large quantities of viable islets that must be separated from the highly immunogenic exocrine tissue and because handpicking is too time-consuming and laborious to be clinically relevant, a new approach for solving this problem has been established in rat models....

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.1.s146

    authors: Winoto-Morbach S,Ulrichs K,Leyhausen G,Müller-Ruchholtz W

    更新日期:1989-01-01 00:00:00

  • Developmental-stage-dependent teratogenic effects of maternal spontaneous diabetes in the chinese hamster.

    abstract::The effect of maternal diabetes on teratogenesis was examined utilizing female Chinese hamsters with typical diabetic symptoms from our closed colony (CHA) and F13-F19 of the brother-sister mating generations of a diabetic strain (CHAD). Both groups were mated with nondiabetic males from CHA. Embryologic studies on da...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.32.7.637

    authors: Funaki K,Mikamo K

    更新日期:1983-07-01 00:00:00

  • Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes.

    abstract::Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donor...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1281

    authors: Anquetil F,Mondanelli G,Gonzalez N,Rodriguez Calvo T,Zapardiel Gonzalo J,Krogvold L,Dahl-Jørgensen K,Van den Eynde B,Orabona C,Grohmann U,von Herrath MG

    更新日期:2018-09-01 00:00:00

  • Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity.

    abstract::Diabetic states are characterized by a raised serum/islet level of triglycerides and a lowered EC50 (concentration at half-maximal stimulation) for glucose-induced insulin secretion. Culturing islets with long-chain fatty acids (FAs) replicates the basal insulin hypersecretion. In a previous study, we showed that the ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.12.1889

    authors: Liu YQ,Tornheim K,Leahy JL

    更新日期:1998-12-01 00:00:00

  • The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats.

    abstract::Acute elevations of plasma free fatty acid (FFA) levels augment glucose-stimulated insulin secretion (GSIS). Prolonged elevations of FFA levels reportedly impair GSIS, but no one has previously compared GSIS after prolonged exposure to saturated or unsaturated fat. Rats received a low-fat diet (Low-Fat) or one enriche...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.6.1825

    authors: Dobbins RL,Szczepaniak LS,Myhill J,Tamura Y,Uchino H,Giacca A,McGarry JD

    更新日期:2002-06-01 00:00:00

  • Acetylsalicyclic acid restores acute insulin response reduced by furosemide in man.

    abstract::Prostaglandin E (PGE) infusion in normal man inhibits the acute insulin response to glucose. In order to determine whether endogenously released PGE might also inhibit insulin secretion, glucose-stimulated insulin responses were investigated in normal volunteers after furosemide (40 mg i.v.), a stimulator of endogenou...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.9.841

    authors: Giugliano D,Torella R,Sgambato S,D'Onofrio F

    更新日期:1979-09-01 00:00:00

  • Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase.

    abstract::This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose redu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.7.1851

    authors: Price SA,Agthong S,Middlemas AB,Tomlinson DR

    更新日期:2004-07-01 00:00:00

  • Identification of tyrosine phosphatase 2(256-760) construct as a new, sensitive marker for the detection of islet autoimmunity in type 2 diabetic patients: the non-insulin requiring autoimmune diabetes (NIRAD) study 2.

    abstract:OBJECTIVE:The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasia...

    journal_title:Diabetes

    pub_type: 杂志文章,多中心研究

    doi:10.2337/db07-0874

    authors: Tiberti C,Giordano C,Locatelli M,Bosi E,Bottazzo GF,Buzzetti R,Cucinotta D,Galluzzo A,Falorni A,Dotta F

    更新日期:2008-05-01 00:00:00

  • Localization of the O-linked N-acetylglucosamine transferase in rat pancreas.

    abstract::O-linked N-acetylglucosamine transferase (OGT) catalyzes the attachment ofN-acetylglucosamine (GlcNAc) monosaccharides to the hydroxyl group of serine or threonine residues of intracellular proteins and may play an important role in the hexosamine pathway. Glucose-induced insulin resistance is mediated by increased ac...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.12.2407

    authors: Akimoto Y,Kreppel LK,Hirano H,Hart GW

    更新日期:1999-12-01 00:00:00

  • Differential effect of the antidiabetic thiazolidinediones troglitazone and pioglitazone on human platelet aggregation mechanism.

    abstract::Troglitazone and pioglitazone, antidiabetic thiazolidinediones, are known to improve insulin resistance. However, the effect of these drugs on platelet aggregation remains unclear. The chemical structure of troglitazone contains vitamin E. Accordingly, we studied the effect of troglitazone, pioglitazone, and vitamin E...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.9.1494

    authors: Ishizuka T,Itaya S,Wada H,Ishizawa M,Kimura M,Kajita K,Kanoh Y,Miura A,Muto N,Yasuda K

    更新日期:1998-09-01 00:00:00

  • Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

    abstract::Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that s...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.8.2110

    authors: Babaei-Jadidi R,Karachalias N,Ahmed N,Battah S,Thornalley PJ

    更新日期:2003-08-01 00:00:00

  • Dual effects of veratridine on glucagon and insulin secretion: dependence upon extracellular and intracellular calcium.

    abstract::The stimulatory effect of the sodium ionophore, veratridine (10, 25 and 50 microM), on glucagon and insulin secretion was investigated using monolayer cultures of newborn rat pancreas. The results suggest that intracellular accumulation of sodium modulates hormone secretion from both alpha- and beta-cells. The action ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.5.446

    authors: Kawazu S,Ikeuchi M,Kikuchi M,Kanazawa Y,Fujimoto WY,Kosaka K

    更新日期:1981-05-01 00:00:00

  • Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation.

    abstract:OBJECTIVE:Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. RESEARCH DESIGN AND METHODS:Forearm skeletal musc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0857

    authors: Jocken JW,Roepstorff C,Goossens GH,van der Baan P,van Baak M,Saris WH,Kiens B,Blaak EE

    更新日期:2008-07-01 00:00:00

  • Residual insulin production and pancreatic ß-cell turnover after 50 years of diabetes: Joslin Medalist Study.

    abstract:OBJECTIVE:To evaluate the extent of pancreatic β-cell function in a large number of insulin-dependent diabetic patients with a disease duration of 50 years or longer (Medalists). RESEARCH DESIGN AND METHODS:Characterization of clinical and biochemical parameters and β-cell function of 411 Medalists with correlation wi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0676

    authors: Keenan HA,Sun JK,Levine J,Doria A,Aiello LP,Eisenbarth G,Bonner-Weir S,King GL

    更新日期:2010-11-01 00:00:00

  • Oral vanadate reduces Na(+)-dependent glucose transport in rat small intestine.

    abstract::The effects of oral vanadate supplementation on intestinal morphometry and glucose transport were examined in STZ-induced diabetic and age-matched control male Sprague-Dawley rats. Animals received 0.1 mg/ml vanadium pentoxide in their drinking water over 14 days. Vanadate reduced intestinal glucose maximal transport ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.8.1126

    authors: Madsen KL,Porter VM,Fedorak RN

    更新日期:1993-08-01 00:00:00

  • The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report.

    abstract::This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (T...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-0261

    authors: Krischer JP,Liu X,Lernmark Å,Hagopian WA,Rewers MJ,She JX,Toppari J,Ziegler AG,Akolkar B,TEDDY Study Group.

    更新日期:2017-12-01 00:00:00

  • Role of the fatty acid binding protein mal1 in obesity and insulin resistance.

    abstract::The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.2.300

    authors: Maeda K,Uysal KT,Makowski L,Görgün CZ,Atsumi G,Parker RA,Brüning J,Hertzel AV,Bernlohr DA,Hotamisligil GS

    更新日期:2003-02-01 00:00:00

  • Overexpression of monocarboxylate transporter-1 (SLC16A1) in mouse pancreatic β-cells leads to relative hyperinsulinism during exercise.

    abstract::Exercise-induced hyperinsulinism (EIHI) is an autosomal dominant disorder characterized by inappropriate insulin secretion in response to vigorous physical exercise or pyruvate injection. Activating mutations in the monocarboxylate transporter-1 (MCT1, SLC16A1) promoter have been linked to EIHI. Expression of this pyr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1531

    authors: Pullen TJ,Sylow L,Sun G,Halestrap AP,Richter EA,Rutter GA

    更新日期:2012-07-01 00:00:00

  • Aldose reductase inhibition and glomerular abnormalities in diabetic rats.

    abstract::We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment w...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.8.981

    authors: Daniels BS,Hostetter TH

    更新日期:1989-08-01 00:00:00

  • Limited acute influences of electrical baroreceptor activation on insulin sensitivity and glucose delivery: a randomized, double-blind, crossover clinical study.

    abstract::Arterial baroreflexes may regulate resistance vessels supplying glucose to skeletal muscle by modulating efferent sympathetic nervous system activity. We hypothesized that selective manipulation of baroreflex activity through electrical carotid sinus stimulation influences insulin sensitivity by changing muscular gluc...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db13-1651

    authors: May M,Ahrens J,Menne J,Haller H,Beige J,Eckert S,Jordan J,Engeli S

    更新日期:2014-08-01 00:00:00

  • Coordinate phosphorylation of insulin-receptor kinase and its 175,000-Mr endogenous substrate in rat hepatocytes.

    abstract::To investigate the early events in insulin signal transmission in liver, isolated rat hepatocytes were labeled with 32P, and proteins phosphorylated in response to insulin were detected by immunoprecipitation with anti-phosphotyrosine and anti-receptor antibodies and analyzed by sodium dodecyl sulfate (SDS)-polyacryla...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.1.66

    authors: Okamoto M,Karasik A,White MF,Kahn CR

    更新日期:1991-01-01 00:00:00

  • Multiple redox forms of the insulin receptor in native liver membranes.

    abstract::Three forms of disulfide-linked insulin receptor complexes are labeled by covalent cross-linking to receptor-bound 125I-insulin in native adipocyte or liver membranes. These receptors of Mr 350,000 Mr 320,000, and Mr 290,000 are composed of alpha (Mr 125,000), beta(Mr 90,000), and beta 1(Mr 49,000) subunits in stoichi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.29.11.945

    authors: Massaqué J,Czech MP

    更新日期:1980-11-01 00:00:00

  • TBC1D4 Is Necessary for Enhancing Muscle Insulin Sensitivity in Response to AICAR and Contraction.

    abstract::Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. We recently demonstrated that AMPK is necessary for AICAR, contraction, and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent ske...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0769

    authors: Kjøbsted R,Chadt A,Jørgensen NO,Kido K,Larsen JK,de Wendt C,Al-Hasani H,Wojtaszewski JFP

    更新日期:2019-09-01 00:00:00

  • Intestinal sugar transport in experimental diabetes.

    abstract::The increased sugar transport was examined in the isolated small intestine of streptozotocin-diabetic rats. In the small intestine of these animals, the rate of glucose absorption in vivo is slightly increased, but not that of galactose of 3-O-MG (3-O-Methylglucose); however, in the isolated small intestine, the mucos...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.7.568

    authors: Csáky TZ,Fischer E

    更新日期:1981-07-01 00:00:00

  • Effects of pioglitazone on suppressor of cytokine signaling 3 expression: potential mechanisms for its effects on insulin sensitivity and adiponectin expression.

    abstract::Pioglitazone is widely used for the treatment of diabetic patients with insulin resistance. The mechanism of pioglitazone to improve insulin sensitivity is not fully understood. Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistanc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1039

    authors: Kanatani Y,Usui I,Ishizuka K,Bukhari A,Fujisaka S,Urakaze M,Haruta T,Kishimoto T,Naka T,Kobayashi M

    更新日期:2007-03-01 00:00:00

  • Histologic differentiation of human fetal pancreatic explants transplanted into nude mice.

    abstract::The transplantation of human fetal pancreas has been suggested as a means of treatment of insulin-dependent diabetes in man. We have obtained human fetal pancreata during the second trimester of pregnancy and transplanted 1-mm3 explants subcutaneously (s.c.) into both diabetic and nondiabetic nude mice, some of the ti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.12.1180

    authors: Tuch BE,Ng AB,Jones A,Turtle JR

    更新日期:1984-12-01 00:00:00

  • Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

    abstract::A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian B...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.837

    authors: Poulsen PL,Ebbehøj E,Arildsen H,Knudsen ST,Hansen KW,Mølgaard H,Mogensen CE

    更新日期:2001-04-01 00:00:00

  • Targeted Expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High-Fat Diet-Fed Mice.

    abstract::Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0387

    authors: Ryan TE,Schmidt CA,Green TD,Spangenburg EE,Neufer PD,McClung JM

    更新日期:2016-09-01 00:00:00

  • A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

    abstract::Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during th...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0097

    authors: Raubenheimer PJ,Nyirenda MJ,Walker BR

    更新日期:2006-07-01 00:00:00