Blood glucose lowering and glucagonostatic effects of glucagon-like peptide I in insulin-deprived diabetic dogs.

Abstract:

:To establish potential effects of glucagon-like peptide I (GLP-I) on blood glucose control in insulin-deficient states, GLP-I [GLP-I(7-36) amide; 10 pmol x kg(-1) x min(-1)] was infused intravenously in six fasting, canine C-peptide-negative, chronically diabetic dogs for 8 h. Blood samples were saved for the analysis of hormones, metabolites, and turnover rates of glucose (6-(3)H-glucose), alanine (U-(14)C-alanine), and urea ((15)N(2)-urea) starting 22 h after the last subcutaneous dose of exogenous insulin. Circulating plasma GLP-I levels rose under infusion from 2.9 +/- 0.8 to 41.4 +/- 10.1 pmol/l. This was efficient to significantly reduce the preexisting diabetic hyperglucagonemia. Since in the utilized model functioning pancreatic beta-cells are lacking, GLP-I had no insulinogenic effect. Compared with control experiments in the same animals receiving saline infusion, glycemia dropped from 20.8 +/- 1.9 to 16.2 +/- 1.0 mmol/l (P < 0.05). This was in parallel to the infusion of GLP-I and was most likely caused by a decrease of elevated glucose production since overall glucose turnover decreased with no alteration in glucose metabolic clearance. Alanine turnover was significantly reduced, obviously reflecting a decline in alanine production in relation to changed muscle glucose uptake under conditions of lower glycemia and overall glucose turnover. There was, however, neither an effect of GLP-I on alanine conversion into circulating glucose nor an effect on urea production rate, indicating unchanged gluconeogenesis from amino acid precursors. We conclude that the blood glucose-lowering effect of GLP-I in an animal model of insulinopenia was shown to be due to a reduction in hepatic glucose output, possibly secondary to reduction in glucagon concentrations leading to decreased glycogenolysis. Whether GLP-I might be therapeutically useful in clinical insulin-deficient diabetes needs to be verified.

journal_name

Diabetes

journal_title

Diabetes

authors

Freyse EJ,Becher T,El-Hag O,Knospe S,Göke B,Fischer U

doi

10.2337/diab.46.5.824

subject

Has Abstract

pub_date

1997-05-01 00:00:00

pages

824-8

issue

5

eissn

0012-1797

issn

1939-327X

journal_volume

46

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

    abstract::Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 mont...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db16-0823

    authors: Haller MJ,Gitelman SE,Gottlieb PA,Michels AW,Perry DJ,Schultz AR,Hulme MA,Shuster JJ,Zou B,Wasserfall CH,Posgai AL,Mathews CE,Brusko TM,Atkinson MA,Schatz DA

    更新日期:2016-12-01 00:00:00

  • Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications.

    abstract::Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is probably determined by renal hemodynamic abnormalities and by a genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angioten...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.3.384

    authors: Marre M,Bernadet P,Gallois Y,Savagner F,Guyene TT,Hallab M,Cambien F,Passa P,Alhenc-Gelas F

    更新日期:1994-03-01 00:00:00

  • Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease.

    abstract::Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.2.237

    authors: Kallmann BA,Hüther M,Tubes M,Feldkamp J,Bertrams J,Gries FA,Lampeter EF,Kolb H

    更新日期:1997-02-01 00:00:00

  • No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-L1 adipocytes.

    abstract::Membrane glycoprotein plasma cell 1 (PC-1) has been shown to be increased in type 2 diabetes and involved in insulin resistance through inhibiting the insulin receptor tyrosine kinase, which was demonstrated using cultured breast cancer cells. However, other reports have shown contradictory results in Chinese hamster ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.7.1365

    authors: Sakoda H,Ogihara T,Anai M,Funaki M,Inukai K,Katagiri H,Fukushima Y,Onishi Y,Ono H,Yazaki Y,Kikuchi M,Oka Y,Asano T

    更新日期:1999-07-01 00:00:00

  • Hypoglycemia-associated changes in the electroencephalogram in patients with type 1 diabetes and normal hypoglycemia awareness or unawareness.

    abstract::Hypoglycemia is associated with increased activity in the low-frequency bands in the electroencephalogram (EEG). We investigated whether hypoglycemia awareness and unawareness are associated with different hypoglycemia-associated EEG changes in patients with type 1 diabetes. Twenty-four patients participated in the st...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db14-1359

    authors: Sejling AS,Kjær TW,Pedersen-Bjergaard U,Diemar SS,Frandsen CS,Hilsted L,Faber J,Holst JJ,Tarnow L,Nielsen MN,Remvig LS,Thorsteinsson B,Juhl CB

    更新日期:2015-05-01 00:00:00

  • The role of melanocortin 3 receptor gene in childhood obesity.

    abstract:OBJECTIVE:Melanocortin 3 receptor (MC3R) plays a critical role in weight regulation of rodents, but its role in humans remains unclear. The objective of this study was to identify genetic variants of the MC3R gene and determine its association with childhood obesity. RESEARCH DESIGN AND METHODS:We screened 201 obese c...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0225

    authors: Lee YS,Poh LK,Kek BL,Loke KY

    更新日期:2007-10-01 00:00:00

  • Are the beta-cell signaling molecules malonyl-CoA and cystolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?

    abstract::Widely held theories of the pathogenesis of obesity-associated NIDDM have implicated apparently incompatible events as seminal: 1) insulin resistance in muscle, 2) abnormal secretion of insulin, and 3) increases in intra-abdominal fat. Altered circulating or tissue lipids are characteristic features of obesity and NID...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.45.3.273

    authors: Prentki M,Corkey BE

    更新日期:1996-03-01 00:00:00

  • 6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin.

    abstract::Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.26.9.857

    authors: Akhtar MS,Verspohl E,Hegner D,Ammon HP

    更新日期:1977-09-01 00:00:00

  • Structure, activation, and biology of calpain.

    abstract::Variation in the calpain 10 gene has recently been shown to be associated with type 2 diabetes by positional cloning. Since then, studies on calpain 10 have been started in correlation with diabetes and insulin-mediated signaling. In this review, the activation mechanism of calpain by calcium ions, which is essential ...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diabetes.53.2007.s12

    authors: Suzuki K,Hata S,Kawabata Y,Sorimachi H

    更新日期:2004-02-01 00:00:00

  • 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

  • Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility.

    abstract::Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistan...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.3.688

    authors: Lan H,Rabaglia ME,Stoehr JP,Nadler ST,Schueler KL,Zou F,Yandell BS,Attie AD

    更新日期:2003-03-01 00:00:00

  • Regulation and function of the muscle glycogen-targeting subunit of protein phosphatase 1 (GM) in human muscle cells depends on the COOH-terminal region and glycogen content.

    abstract::G(M), the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1) targeted to the sarcoplasmic reticulum, was proposed to regulate recovery of glycogen in exercised muscle, whereas mutation truncation of its COOH-terminal domain is known to be associated with type 2 diabetes. Here, we demonstrate dif...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.9.2221

    authors: Lerín C,Montell E,Nolasco T,Clark C,Brady MJ,Newgard CB,Gómez-Foix AM

    更新日期:2003-09-01 00:00:00

  • A Ser311Cys mutation in the human dopamine receptor D2 gene is associated with reduced energy expenditure.

    abstract::Brain dopaminergic pathways play a major role in the control of movement. Absence of the murine dopamine D2 receptor gene (drd2) produces bradykinesia and hypothermia. A Ser311Cys mutation of the human DRD2 produces a marked functional impairment of the receptor and is associated with higher BMI in some populations. W...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.4.901

    authors: Tataranni PA,Baier L,Jenkinson C,Harper I,Del Parigi A,Bogardus C

    更新日期:2001-04-01 00:00:00

  • Sialylated form of the neural cell adhesion molecule (NCAM): a new tool for the identification and sorting of beta-cell subpopulations with different functional activity.

    abstract::To clarify the relationship between variations in beta-cell mass and pancreatic function, we investigated the possibility to analyze, quantify, and sort beta-cell subpopulations with different functional maturity. To this aim, we tested the reliability of the sialylated form of neural cell adhesion molecule (NCAM) (PS...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.2007.s125

    authors: Bernard-Kargar C,Kassis N,Berthault MF,Pralong W,Ktorza A

    更新日期:2001-02-01 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

  • Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.

    abstract:OBJECTIVE:Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary hu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0583

    authors: Bouzakri K,Austin R,Rune A,Lassman ME,Garcia-Roves PM,Berger JP,Krook A,Chibalin AV,Zhang BB,Zierath JR

    更新日期:2008-06-01 00:00:00

  • Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan.

    abstract::Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-1238

    authors: Saeed S,Arslan M,Manzoor J,Din SM,Janjua QM,Ayesha H,Ain QT,Inam L,Lobbens S,Vaillant E,Durand E,Derhourhi M,Amanzougarene S,Badreddine A,Berberian L,Gaget S,Khan WI,Butt TA,Bonnefond A,Froguel P

    更新日期:2020-07-01 00:00:00

  • The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates.

    abstract::Increased pancreas mass and glucagon-positive adenomas have been suggested to be a risk associated with sitagliptin or exenatide therapy in humans. Novo Nordisk has conducted extensive toxicology studies, including data on pancreas weight and histology, in Cynomolgus monkeys dosed with two different human glucagon-lik...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1087

    authors: Gotfredsen CF,Mølck AM,Thorup I,Nyborg NC,Salanti Z,Knudsen LB,Larsen MO

    更新日期:2014-07-01 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

  • 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

  • Plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) after evisceration with and without a functional liver.

    abstract::Fed male Wistar rats were eviscerated by two procedures. The first group of eviscerated rats were left with a nonfunctional liver in situ while the second group were eviscerated by a newer technic, developed in this laboratory, that preserves liver function. The animals were maintained on a regimen of saline and antib...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.7.637

    authors: Penhos JC,Ezequiel M,Lepp A,Ramey ER

    更新日期:1975-07-01 00:00:00

  • Programming of islet functions in the progeny of hyperinsulinemic/obese rats.

    abstract::Neonatal female rat pups that were raised artificially on a high-carbohydrate (HC) milk formula during their suckling period developed hyperinsulinemia immediately, maintained chronic hyperinsulinemia in the postweaning period on laboratory diet, and developed obesity in adulthood. Pups (second-generation HC [2-HC]) b...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.4.984

    authors: Srinivasan M,Aalinkeel R,Song F,Patel MS

    更新日期:2003-04-01 00:00:00

  • Carotid artery intima-media thickness in children with type 1 diabetes.

    abstract::Postmortem studies have shown a relationship between diabetic state and atherosclerotic arterial lesions in adolescents. The aim of the present study was to determine the presence of increased subclinical atherosclerosis (measured as carotid intima-media thickness [IMT]) and its risk factors, including lipoprotein oxi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.2.493

    authors: Järvisalo MJ,Putto-Laurila A,Jartti L,Lehtimäki T,Solakivi T,Rönnemaa T,Raitakari OT

    更新日期:2002-02-01 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

  • The functional state of sympathetic nerves in spontaneously diabetic mice.

    abstract::I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks ol...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.27.10.969

    authors: Giachetti A

    更新日期:1978-10-01 00:00:00

  • Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis.

    abstract::The Dio2 gene encodes the type 2 deiodinase (D2) that activates thyroxine (T4) to 3,3',5-triiodothyronine (T3), the disruption of which (Dio2(-/-)) results in brown adipose tissue (BAT)-specific hypothyroidism in an otherwise euthyroid animal. In the present studies, cold exposure increased Dio2(-/-) BAT sympathetic s...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.3.577

    authors: Christoffolete MA,Linardi CC,de Jesus L,Ebina KN,Carvalho SD,Ribeiro MO,Rabelo R,Curcio C,Martins L,Kimura ET,Bianco AC

    更新日期:2004-03-01 00:00:00

  • Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats.

    abstract::Diet-induced obesity is known to cause peripheral insulin resistance in rodents. We have recently found that feeding cod protein to high-fat-fed rats prevents the development of insulin resistance in skeletal muscle. In the present study, we have further explored the cellular mechanisms behind this beneficial effect o...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.1.29

    authors: Tremblay F,Lavigne C,Jacques H,Marette A

    更新日期:2003-01-01 00:00:00

  • Large GLUT4 vesicles are stationary while locally and reversibly depleted during transient insulin stimulation of skeletal muscle of living mice: imaging analysis of GLUT4-enhanced green fluorescent protein vesicle dynamics.

    abstract:OBJECTIVE:Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subseq...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-1578

    authors: Lauritzen HP,Galbo H,Brandauer J,Goodyear LJ,Ploug T

    更新日期:2008-02-01 00:00:00

  • Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients.

    abstract::To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjec...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.44.11.1318

    authors: Trovati M,Mularoni EM,Burzacca S,Ponziani MC,Massucco P,Mattiello L,Piretto V,Cavalot F,Anfossi G

    更新日期:1995-11-01 00:00:00

  • Value of antibodies to islet protein tyrosine phosphatase-like molecule in predicting type 1 diabetes.

    abstract::Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.8.1270

    authors: Hawa M,Rowe R,Lan MS,Notkins AL,Pozzilli P,Christie MR,Leslie RD

    更新日期:1997-08-01 00:00:00