Elimination of glucagon-like peptide 1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action.

Abstract:

:Leptin and glucagon-like peptide 1 (GLP-1) exhibit opposing actions in the endocrine pancreas. GLP-1 stimulates insulin biosynthesis, secretion, and islet growth, whereas leptin inhibits glucose-dependent insulin secretion and insulin gene transcription. In contrast, GLP-1 and leptin actions overlap in the central nervous system, where leptin has been shown to activate GLP-1 circuits that inhibit food intake. To determine the physiological importance of GLP-1 receptor (GLP-1R)-leptin interactions, we studied islet function and feeding behavior in ob/ob:GLP-1R(-/-) mice. Although GLP-1R actions are thought to be essential for glucose-dependent insulin secretion, the levels of fasting glucose, glycemic excursion after glucose loading, glucose-stimulated insulin, and pancreatic insulin RNA content were similar in ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R(-/-) mice. Despite evidence linking GLP-1R signaling to the regulation of islet neogenesis and proliferation, ob/ob:GLP-1R(-/-) mice exhibited significantly increased islet numbers and area and an increase in the number of large islets compared with GLP-1R(+/+) or (-/-) mice (P < -0.01 to 0.05). Similarly, growth rates and both shortand long-term control of food intake were comparable in ob/ob:GLP-1R(+/+) versus ob/ob:GLP-1R4(-/-) mice. Furthermore, leptin produced a similar inhibition of food intake in GLP-1R(-/-), ob/ob:GLP-1R(+/+), and ob/ob:GLP1R4(-/-) mice. These findings illustrate that although leptin and GLP-1 actions overlap in the brain and endocrine pancreas, disruption of GLP-1 signaling does not modify the response to leptin or the phenotype of leptin deficiency in the ob/ob mouse, as assessed by long-term control of body weight or the adaptive beta-cell response to insulin resistance in vivo.

journal_name

Diabetes

journal_title

Diabetes

authors

Scrocchi LA,Hill ME,Saleh J,Perkins B,Drucker DJ

doi

10.2337/diabetes.49.9.1552

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1552-60

issue

9

eissn

0012-1797

issn

1939-327X

journal_volume

49

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Minimal effects of phorbol esters on glucose transport and insulin sensitivity of rat skeletal muscle.

    abstract::Protein kinase C (PKC) has been suggested as a mediator of insulin's effect on glucose transport, and PKC-mediated modulation of tyrosine kinase activity in the insulin receptor has been implicated in regulating the insulin sensitivity of tissues. Because skeletal muscle is a major target of insulin action, we examine...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.5.499

    authors: Sowell MO,Treutelaar MK,Burant CF,Buse MG

    更新日期:1988-05-01 00:00:00

  • Hyperglycemia suppresses the adrenal medullary response to hypoxemia.

    abstract::An in vivo microdialysis technique was used to study adrenal medullary function in 6 euglycemic and 6 hyperglycemic anesthetized Sprague-Dawley rats exposed to hypoxia. After stabilization of an adrenal dialysis probe, dialyzable adrenal epinephrine and norepinephrine were measured in response to 15 min of 7.8% oxygen...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.5.645

    authors: Cohen WR,Deutsch J

    更新日期:1994-05-01 00:00:00

  • Intrinsic differences in adipocyte precursor cells from different white fat depots.

    abstract::Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1753

    authors: Macotela Y,Emanuelli B,Mori MA,Gesta S,Schulz TJ,Tseng YH,Kahn CR

    更新日期:2012-07-01 00:00:00

  • Association analysis of 29,956 individuals confirms that a low-frequency variant at CCND2 halves the risk of type 2 diabetes by enhancing insulin secretion.

    abstract::A recent study identified a low-frequency variant at CCND2 associated with lower risk of type 2 diabetes, enhanced insulin response to a glucose challenge, higher height, and, paradoxically, higher BMI. We aimed to replicate the strength and effect size of these associations in independent samples and to assess the un...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-1456

    authors: Yaghootkar H,Stancáková A,Freathy RM,Vangipurapu J,Weedon MN,Xie W,Wood AR,Ferrannini E,Mari A,Ring SM,Lawlor DA,Davey Smith G,Jørgensen T,Hansen T,Pedersen O,Steinthorsdottir V,Guðbjartsson DF,Thorleifsson G,Thorstei

    更新日期:2015-06-01 00:00:00

  • Diabetes and the myo-inositol paradox.

    abstract::To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.39.10.1305

    authors: Loy A,Lurie KG,Ghosh A,Wilson JM,MacGregor LC,Matschinsky FM

    更新日期:1990-10-01 00:00:00

  • Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia.

    abstract::Elevation of glucagon levels and increase in α-cell mass are associated with states of hyperglycemia in diabetes. Our previous studies have highlighted the role of nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls glucagon secretion and α-cell mass. In the current studies we investigated the effe...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db20-0440

    authors: Bozadjieva Kramer N,Lubaczeuski C,Blandino-Rosano M,Barker G,Gittes GK,Caicedo A,Bernal-Mizrachi E

    更新日期:2021-02-01 00:00:00

  • Influence of circulating epinephrine on absorption of subcutaneously injected insulin.

    abstract::Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; health...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.6.694

    authors: Fernqvist E,Gunnarsson R,Linde B

    更新日期:1988-06-01 00:00:00

  • Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells.

    abstract::Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.6.1737

    authors: Shojima N,Sakoda H,Ogihara T,Fujishiro M,Katagiri H,Anai M,Onishi Y,Ono H,Inukai K,Abe M,Fukushima Y,Kikuchi M,Oka Y,Asano T

    更新日期:2002-06-01 00:00:00

  • Function and Mechanism of Long Noncoding RNAs in Adipocyte Biology.

    abstract::The last two decades have witnessed an explosion of interest in adipocyte biology, coinciding with the upsurge of obesity and metabolic syndrome. Now we have new perspectives on the distinct developmental origins of white, brown, and beige adipocytes and their role in metabolic physiology and disease. Beyond fuel meta...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/dbi18-0009

    authors: Sun L,Lin JD

    更新日期:2019-05-01 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

  • The hemodynamic abnormalities in short-term insulin deficiency: the role of prostaglandin inhibition.

    abstract::It has been suggested that the hemodynamic derangements present in diabetic ketoacidosis are the results not only of profound volume depletion but also of the effects of increased production of vasodilating prostaglandins (PGs), principally PGI2, released by adipose tissue. In animal and in vitro models, prostaglandin...

    journal_title:Diabetes

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2337/diab.45.5.602

    authors: Avogaro A,Crepaldi C,Piarulli F,Milan D,Valerio A,Pavan P,Sacerdoti D,Calabrò A,Macdonald I,Crepaldi G,Scognamiglio R,Tiengo A

    更新日期:1996-05-01 00:00:00

  • SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity.

    abstract:OBJECTIVE:Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESI...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1191

    authors: Rutanen J,Yaluri N,Modi S,Pihlajamäki J,Vänttinen M,Itkonen P,Kainulainen S,Yamamoto H,Lagouge M,Sinclair DA,Elliott P,Westphal C,Auwerx J,Laakso M

    更新日期:2010-04-01 00:00:00

  • Altered lysosomal glycohydrolase activities in juvenile diabetes mellitus.

    abstract::Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.5.420

    authors: Bomback FM,Nakagawa S,Kumin S,Nitowsky HM

    更新日期:1976-05-01 00:00:00

  • Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin.

    abstract::It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provides first insight int...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.2.233

    authors: Bosco D,Meda P,Halban PA,Rouiller DG

    更新日期:2000-02-01 00:00:00

  • Identification of an interactive effect of beta3- and alpha2b-adrenoceptor gene polymorphisms on fat mass in Caucasian women.

    abstract::Several adrenoceptor subtypes are expressed in adipocytes, which together exert their influence on adipocyte metabolism. Therefore, we specifically examined the interactive effect of Trp64Arg (beta3) and Glu12/Glu9 (alpha2b) adrenoceptor (AR) polymorphisms on energy metabolism and body composition in healthy women wit...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.1.91

    authors: Dionne IJ,Turner AN,Tchernof A,Pollin TI,Avrithi D,Gray D,Shuldiner AR,Poehlman ET

    更新日期:2001-01-01 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

  • New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients.

    abstract::Effects of oral administration of DG-5128, a new oral hypoglycemic agent, on glycemic control after a mixed meal and an in vivo glucose disposal were measured in subjects with nonobese non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of DG-5128 significantly (P less than .05) enhanced insulin secre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.10.1085

    authors: Kashiwagi A,Harano Y,Suzuki M,Kojima H,Harada M,Nishio Y,Shigeta Y

    更新日期:1986-10-01 00:00:00

  • The cell cycle inhibitory protein p21cip is not essential for maintaining beta-cell cycle arrest or beta-cell function in vivo.

    abstract::p21(cip1), a regulatory molecule upstream of the G(1/0) checkpoint, is increased in beta-cells in response to mitogenic stimulation. Whereas p21(cip1) can variably stimulate or inhibit cell cycle progression, in vitro studies suggest that p21(cip1) acts as an inhibitor in the pancreatic beta-cell. To determine the fun...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0627

    authors: Cozar-Castellano I,Haught M,Stewart AF

    更新日期:2006-12-01 00:00:00

  • Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors.

    abstract::We tested the hypothesis that activation of the protective arm of the renin angiotensin system, the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, corrects the vasoreparative dysfunction typically seen in the CD34(+) cells isolated from diabetic individuals. Peripheral blood CD...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0808

    authors: Jarajapu YP,Bhatwadekar AD,Caballero S,Hazra S,Shenoy V,Medina R,Kent D,Stitt AW,Thut C,Finney EM,Raizada MK,Grant MB

    更新日期:2013-04-01 00:00:00

  • The novel therapeutic effect of phosphoinositide 3-kinase-γ inhibitor AS605240 in autoimmune diabetes.

    abstract::Type 1 diabetes (T1D) remains a major health problem worldwide, with a steadily rising incidence yet no cure. Phosphoinositide 3-kinase-γ (PI3Kγ), a member of a family of lipid kinases expressed primarily in leukocytes, has been the subject of substantial research for its role in inflammatory diseases. However, the ro...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0134

    authors: Azzi J,Moore RF,Elyaman W,Mounayar M,El Haddad N,Yang S,Jurewicz M,Takakura A,Petrelli A,Fiorina P,Ruckle T,Abdi R

    更新日期:2012-06-01 00:00:00

  • Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1 diabetes.

    abstract::This article examines the role of the autonomic nervous system in mediating the increase of glucagon secretion observed during insulin-induced hypoglycemia (IIH). In the first section, we briefly review the importance of the alpha-cell response in recovery from hypoglycemia under both physiologic conditions and pathop...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.47.7.995

    authors: Taborsky GJ Jr,Ahrén B,Havel PJ

    更新日期:1998-07-01 00:00:00

  • Validation of 111In-Exendin SPECT for the Determination of the β-Cell Mass in BioBreeding Diabetes-Prone Rats.

    abstract::The changes in β-cell mass (BCM) during the development and progression of diabetes could potentially be measured by radionuclide imaging using radiolabeled exendin. In this study, we investigated the potential of 111In-diethylenetriaminepentaacetic acid-exendin-3 (111In-exendin) in a rat model that closely mimics the...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db17-1312

    authors: Brom M,Joosten L,Frielink C,Peeters H,Bos D,van Zanten M,Boerman O,Gotthardt M

    更新日期:2018-10-01 00:00:00

  • Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats.

    abstract::We reported earlier that β-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats wit...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0357

    authors: Mahadevan J,Parazzoli S,Oseid E,Hertzel AV,Bernlohr DA,Vallerie SN,Liu CQ,Lopez M,Harmon JS,Robertson RP

    更新日期:2013-10-01 00:00:00

  • Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides.

    abstract::The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.3.301

    authors: Gordon EE,Duga J

    更新日期:1975-03-01 00:00:00

  • Monocyte gene-expression profiles associated with childhood-onset type 1 diabetes and disease risk: a study of identical twins.

    abstract:OBJECTIVE:Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, b...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db09-1433

    authors: Beyan H,Drexhage RC,van der Heul Nieuwenhuijsen L,de Wit H,Padmos RC,Schloot NC,Drexhage HA,Leslie RD

    更新日期:2010-07-01 00:00:00

  • Epinephrine enhancement of potassium-stimulated immunoreactive insulin secretion. Role of beta-adrenergic receptors.

    abstract::Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secre...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.27.5.550

    authors: Hiatt N,Davidson MB,Chapman LW,Sheinkopf JA

    更新日期:1978-05-01 00:00:00

  • Insulin-stimulated glucose disposal increases with time in patients with non-insulin-dependent diabetes mellitus.

    abstract::The relative effects of time versus ambient glucose concentration on insulin-stimulated glucose uptake was estimated by performing 5-h insulin clamp studies in patients with NIDDM. Each experimental subject was studied three times, at steady-state plasma insulin levels approximately 2000 microU/ml, but at different st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.7.643

    authors: Liu G,Chen YD,Hollenbeck CB,Lardinois CK,Reaven GM

    更新日期:1984-07-01 00:00:00

  • Sex-discordant associations with adiponectin levels and lipid profiles in children.

    abstract::In adults, lower circulating levels of the adipocyte-derived hormone adiponectin are associated with obesity, type 2 diabetes, and cardiovascular disease risks. Its use as a risk marker in children is less clear. In 839 children aged 8 years from a representative birth cohort, circulating adiponectin levels were assoc...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db05-1272

    authors: Ong KK,Frystyk J,Flyvbjerg A,Petry CJ,Ness A,Dunger DB

    更新日期:2006-05-01 00:00:00

  • Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes.

    abstract::Although decreased levels of circulating insulinlike growth factor I (IGF-I) and hepatic IGF-I mRNA in diabetic animal models support a role for insulin in IGF-I regulation, it has been difficult to study the effects of insulin in vitro. Few immortal cell lines exhibit hormone-responsive production of IGF-I, and studi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.11.1525

    authors: Phillips LS,Goldstein S,Pao CI

    更新日期:1991-11-01 00:00:00

  • Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease.

    abstract::The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of r...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/db16-0796

    authors: Gilbert RE

    更新日期:2017-04-01 00:00:00