Diet-induced obesity prevents interstitial dispersion of insulin in skeletal muscle.

Abstract:

OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake. When insulin resistance is induced by exogenous lipid infusion, this interstitial diffusion process is curtailed. Thus, the possibility exists that hyperlipidemia, such as that seen during obesity, may inhibit insulin action to muscle cells and exacerbate insulin resistance. Here we asked whether interstitial insulin diffusion is reduced in physiological obesity induced by a high-fat diet (HFD). RESEARCH DESIGN AND METHODS:Dogs were fed a regular diet (lean) or one supplemented with bacon grease for 9-12 weeks (HFD). Basal insulin (0.2 mU x min(-1) x kg(-1)) euglycemic clamps were performed on fat-fed animals (n = 6). During clamps performed under anesthesia, five sequential doses of insulin were injected into the vastus medialis of one hind limb (INJ); the contralateral limb (NINJ) served as a control. RESULTS:INJ lymph insulin showed an increase above NINJ in lean animals, but no change in HFD-fed animals. Muscle glucose uptake observed in lean animals did not occur in HFD-fed animals. CONCLUSIONS:Insulin resistance induced by HFD caused a failure of intramuscularly injected insulin to diffuse through the interstitial space and failure to cause glucose uptake, compared with normal animals. High-fat feeding prevents the appearance of injected insulin in the interstitial space, thus reducing binding to skeletal muscle cells and glucose uptake.

journal_name

Diabetes

journal_title

Diabetes

authors

Kolka CM,Harrison LN,Lottati M,Chiu JD,Kirkman EL,Bergman RN

doi

10.2337/db09-0839

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

619-26

issue

3

eissn

0012-1797

issn

1939-327X

pii

db09-0839

journal_volume

59

pub_type

杂志文章

相关文献

DIABETES文献大全
  • β-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes.

    abstract::Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters w...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1951

    authors: Michaliszyn SF,Mari A,Lee S,Bacha F,Tfayli H,Farchoukh L,Ferrannini E,Arslanian S

    更新日期:2014-11-01 00:00:00

  • Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth.

    abstract::Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-contai...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.4.509

    authors: Federoff HJ,Lawrence D,Brownlee M

    更新日期:1993-04-01 00:00:00

  • Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria.

    abstract::The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.6.745

    authors: Gambaro G,Baggio B,Cicerello E,Mastrosimone S,Marzaro G,Borsatti A,Crepaldi G

    更新日期:1988-06-01 00:00:00

  • Pancreatic lipomatosis is a structural marker in nondiabetic children with mutations in carboxyl-ester lipase.

    abstract::Both pancreatic volume reduction and lipomatosis have been observed in subjects with diabetes. The underlying molecular and pathological mechanisms are, however, poorly known, and it has been speculated that both features are secondary to diabetes. We have recently described pancreatic atrophy and lipomatosis in diabe...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0859

    authors: Raeder H,Haldorsen IS,Ersland L,Grüner R,Taxt T,Søvik O,Molven A,Njølstad PR

    更新日期:2007-02-01 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

  • Patients with chronic pancreatitis have islet progenitor cells in their ducts, but reversal of overt diabetes in NOD mice by anti-CD3 shows no evidence for islet regeneration.

    abstract::Monoclonal antibodies to T-cell coreceptors have been shown to tolerise autoreactive T-cells and prevent or even reverse autoimmune pathology. In type 1 diabetes, there is a loss of insulin-secreting beta-cells, and a cure for type 1 diabetes would require not only tolerance induction but also recovery of the function...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db06-0832

    authors: Phillips JM,O'Reilly L,Bland C,Foulis AK,Cooke A

    更新日期:2007-03-01 00:00:00

  • Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout.

    abstract::Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been implicated in the control of blood glucose by its potent effect on expression and signaling of various nuclear receptors. To understand the role of COUP-TFII in glucose homeostasis, conditional COUP-TFII-deficient mice were generated and ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1357

    authors: Bardoux P,Zhang P,Flamez D,Perilhou A,Lavin TA,Tanti JF,Hellemans K,Gomas E,Godard C,Andreelli F,Buccheri MA,Kahn A,Le Marchand-Brustel Y,Burcelin R,Schuit F,Vasseur-Cognet M

    更新日期:2005-05-01 00:00:00

  • Physiological increments in plasma insulin concentrations have selective and different effects on synthesis of hepatic proteins in normal humans.

    abstract::These studies tested the hypothesis that physiological increments in plasma insulin concentrations have selective effects on the synthesis of hepatic proteins in humans. Leucine kinetics and fractional synthetic rates of albumin, fibrinogen, antithrombin III, and apoB-100 were determined in 6 normal subjects, on two d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.42.7.995

    authors: De Feo P,Volpi E,Lucidi P,Cruciani G,Reboldi G,Siepi D,Mannarino E,Santeusanio F,Brunetti P,Bolli GB

    更新日期:1993-07-01 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

  • Interferon-mediated induction of Ia antigen expression on isolated murine whole islets and dispersed islet cells.

    abstract::Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon-gam...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.10.1174

    authors: Wright JR Jr,Lacy PE,Unanue ER,Muszynski C,Hauptfeld V

    更新日期:1986-10-01 00:00:00

  • Lack of association of the polymorphic locus in the 5'-flanking region of the human insulin gene and diabetes in American blacks.

    abstract::A polymorphic region 5' to the human insulin gene has been associated with diabetes in earlier studies. This polymorphic region is composed of tandem repeats that fall into 3 general size classes, designated class 1 (600 base pairs), class 2 (1300 base pairs), and class 3 (2500 base pairs). Frequencies of these classe...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.5.433

    authors: Elbein S,Rotwein P,Permutt MA,Bell GI,Sanz N,Karam JH

    更新日期:1985-05-01 00:00:00

  • v- and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fat

    abstract::Insulin stimulation of adipose and muscle cells results in the translocation of GLUT4 from an intracellular location to the plasma membrane; this translocation is defective in insulin resistance. Studies have suggested an important role for synaptobrevin and syntaxin homologues in this event, particularly the v-solubl...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.4.618

    authors: Maier VH,Melvin DR,Lister CA,Chapman H,Gould GW,Murphy GJ

    更新日期:2000-04-01 00:00:00

  • Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    abstract::Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships betwee...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0407

    authors: Pepino MY,Eisenstein SA,Bischoff AN,Klein S,Moerlein SM,Perlmutter JS,Black KJ,Hershey T

    更新日期:2016-09-01 00:00:00

  • In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance.

    abstract::We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.12.1133

    authors: Blazar BR,Whitley CB,Kitabchi AE,Tsai MY,Santiago J,White N,Stentz FB,Brown DM

    更新日期:1984-12-01 00:00:00

  • Black-white contrasts in insulin levels during pubertal development. The Bogalusa Heart Study.

    abstract::Three hundred and seventy-seven children and adolescents aged 5-17 yr from the biracial (black-white) community of Bogalusa, Louisiana, were evaluated for Tanner stage of sexual development, plasma glucose, and insulin levels during an oral glucose tolerance test. Children of the two races were of similar age, weight,...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.3.313

    authors: Svec F,Nastasi K,Hilton C,Bao W,Srinivasan SR,Berenson GS

    更新日期:1992-03-01 00:00:00

  • Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.

    abstract::The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/db18-0682

    authors: Simó R,Hernández C,Porta M,Bandello F,Grauslund J,Harding SP,Aldington SJ,Egan C,Frydkjaer-Olsen U,García-Arumí J,Gibson J,Lang GE,Lattanzio R,Massin P,Midena E,Ponsati B,Ribeiro L,Scanlon P,Lobo C,Costa MÂ,Cunha-

    更新日期:2019-02-01 00:00:00

  • Glucose regulation of glutaminolysis and its role in insulin secretion.

    abstract::Leucine or the nonmetabolized leucine analog +/- 2-amino-2-norbornane-carboxylic acid (BCH) (both at 10 mmol/l) induced biphasic insulin secretion in the presence of 2 mmol/l glutamine (Q2) in cultured mouse islets pretreated for 40 min without glucose but with Q2 present. The beta-cell response consisted of an initia...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.8.1535

    authors: Gao ZY,Li G,Najafi H,Wolf BA,Matschinsky FM

    更新日期:1999-08-01 00:00:00

  • Sequence variation in PPARG may underlie differential response to troglitazone.

    abstract::Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPARG) agonists used to treat type 2 diabetes. TZDs can also be used to reduce rates of type 2 diabetes in at-risk individuals. However, a large fraction of TZD-treated patients (30-40%) do not respond to TZD treatment with an improvement ...

    journal_title:Diabetes

    pub_type: 杂志文章,随机对照试验

    doi:10.2337/diabetes.54.11.3319

    authors: Wolford JK,Yeatts KA,Dhanjal SK,Black MH,Xiang AH,Buchanan TA,Watanabe RM

    更新日期:2005-11-01 00:00:00

  • Impaired cleavage of preproinsulin signal peptide linked to autosomal-dominant diabetes.

    abstract::Recently, missense mutations upstream of preproinsulin's signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0878

    authors: Liu M,Lara-Lemus R,Shan SO,Wright J,Haataja L,Barbetti F,Guo H,Larkin D,Arvan P

    更新日期:2012-04-01 00:00:00

  • Insulin-pump treatment of pancreas-graft rejection.

    abstract::Continuous subcutaneous insulin infusion (CSII) was combined with antirejection therapy in four diabetic recipients of pancreas and kidney grafts with persisting hyperglycemia due to pancreas rejection. In three of the patients, full function of the pancreas was restored after as many as 40, 86, and 139 days of CSII. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.38.1.s71

    authors: Bartos V,Vanĕk I,Dryáková M,Saudek F,Malý J

    更新日期:1989-01-01 00:00:00

  • "Cytoplasmic" islet cell antibodies. Evidence that the target antigen is a sialoglycoconjugate.

    abstract::We have biochemically treated (periodate, borohydride, neuraminidase, organic solvents) frozen sections of human pancreas and studied the reactivity of islet-cell-antibody-positive human sera and monoclonal antibodies. The autoantigen of pancreatic sections has the properties of sialic acid containing glycolipid. ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.6.617

    authors: Nayak RC,Omar MA,Rabizadeh A,Srikanta S,Eisenbarth GS

    更新日期:1985-06-01 00:00:00

  • Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

    abstract::Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.1.6

    authors: Gold G,Pou J,Gishizky ML,Landahl HD,Grodsky GM

    更新日期:1986-01-01 00:00:00

  • Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves.

    abstract::Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.11.1345

    authors: Gardemann A,Jungermann K,Grosse V,Cossel L,Wohlrab F,Hahn HJ,Blech W,Hildebrandt W

    更新日期:1994-11-01 00:00:00

  • Diabetogenic T-cell clones recognize an altered peptide of chromogranin A.

    abstract::Chromogranin A (ChgA) has been identified as the antigen target for three NOD-derived, diabetogenic CD4 T-cell clones, including the well-known BDC-2.5. These T-cell clones respond weakly to the peptide WE14, a naturally occurring proteolytic cleavage product from ChgA. We show here that WE14 can be converted into a h...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0112

    authors: Delong T,Baker RL,He J,Barbour G,Bradley B,Haskins K

    更新日期:2012-12-01 00:00:00

  • CD5+ B lymphocytes in high-risk islet cell antibody-positive and newly diagnosed IDDM subjects.

    abstract::Human CD5+ B lymphocytes produce autoantibodies that bind to self- and exogenous antigens. Extremely high percentages of CD5+ B lymphocytes are present in the fetal and newborn periods, whereas they constitute only a minority of B lymphocytes in healthy adults. Increased percentages of circulating CD5+ lymphocytes hav...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.10.1314

    authors: Schatz DA,Lang F,Cantor AB,Riley WJ,Maclaren NK,Sleasman JW,Barrett DJ

    更新日期:1991-10-01 00:00:00

  • Hepatic notch signaling correlates with insulin resistance and nonalcoholic fatty liver disease.

    abstract::Hepatic Notch signaling is inappropriately activated in obese/insulin-resistant mouse models. Genetic or pharmacologic inhibition of hepatic Notch signaling in obese mice simultaneously improves glucose tolerance and reduces hepatic triglyceride content. As such, we predicted that Notch signaling in human liver would ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-0769

    authors: Valenti L,Mendoza RM,Rametta R,Maggioni M,Kitajewski C,Shawber CJ,Pajvani UB

    更新日期:2013-12-01 00:00:00

  • Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function.

    abstract::Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) older men (55-75 years old) participated in a s...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-0021

    authors: Murton AJ,Marimuthu K,Mallinson JE,Selby AL,Smith K,Rennie MJ,Greenhaff PL

    更新日期:2015-09-01 00:00:00

  • AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5.

    abstract:OBJECTIVE:Insulin resistance associated with obesity and diabetes is ameliorated by specific overexpression of GLUT4 in skeletal muscle. The molecular mechanisms regulating skeletal muscle GLUT4 expression remain to be elucidated. The purpose of this study was to examine these mechanisms. RESEARCH DESIGN AND METHODS A...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db07-0843

    authors: McGee SL,van Denderen BJ,Howlett KF,Mollica J,Schertzer JD,Kemp BE,Hargreaves M

    更新日期:2008-04-01 00:00:00

  • Variation in the adiponutrin gene influences its expression and associates with obesity.

    abstract::Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is down...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.03.06.db05-1075

    authors: Johansson LE,Hoffstedt J,Parikh H,Carlsson E,Wabitsch M,Bondeson AG,Hedenbro J,Tornqvist H,Groop L,Ridderstråle M

    更新日期:2006-03-01 00:00:00

  • Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines.

    abstract::Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1429

    authors: Mastrandrea LD,Sessanna SM,Laychock SG

    更新日期:2005-05-01 00:00:00