Intramyocellular Ceramides: Subcellular Concentrations and Fractional De Novo Synthesis in Postabsorptive Humans
We investigated the relationship between insulin resistance markers and subsarcolemmal (SS) and intramyofibrillar (IMF) ceramide concentrations, as well as the contribution of plasma palmitate (6.5-h infusion of [U-13C]palmitate) to intramyocellular ceramides. Seventy-six postabsorptive men and women had muscle biopsies 1.5, 6.5, and 24 h after starting the tracer infusion. Concentrations and enrichment of muscle ceramides were measured by liquid chromatography-tandem mass spectrometry. We found that HOMA of insulin resistance, plasma insulin, and triglyceride concentrations were positively correlated with SS C16:0 and C18...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Chung, J. O.; Koutsari, C.; Blachnio-Zabielska, A. U.; Hames, K. C.; Jensen, M. D. Tags: Insulin Action-Cellular and Molecular Metabolism Source Type: research
Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation
We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Lee, H.-Y.; Lee, J. S.; Alves, T.; Ladiges, W.; Rabinovitch, P. S.; Jurczak, M. J.; Choi, C. S.; Shulman, G. I.; Samuel, V. T. Tags: Integrated Physiology-Muscle Metabolism Source Type: research
Some Doubts About the Mantra on the Deleterious Cardiovascular Effects of Sulfonylureas
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Trischitta, V.; Prudente, S. Tags: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes Commentaries Source Type: research
Bait and Trap: Enriching Autoreactive T Cells With {beta}-Cell Antigen-Loading Biomaterial Scaffolds for Early Detection of Type 1 Diabetes
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Fan, Y. Tags: Commentaries Source Type: research
Species-Dependent Mechanisms Regulating Glucose-Dependent GLP-1 Secretion?
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Brubaker, P. L. Tags: Integrated Physiology-Other Hormones Commentaries Source Type: research
In This Issue of Diabetes
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Tags: In This Issue Source Type: research
Comment on Muka et al. Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis. Diabetes 2017;66:577-586
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Abbasi, A. Tags: e-Letters: Comments and Responses Source Type: research
Issues and Events
(Source: Diabetes)
Source: Diabetes - June 21, 2017 Category: Endocrinology Tags: Issues and Events Source Type: research
Statement of Retraction. EGFR Tyrosine Kinase Inhibitor (PD153035) Improves Glucose Tolerance and Insulin Action in High-Fat Diet-Fed Mice. Diabetes 2009;58:2910-2919. DOI: 10.2337/db08-0506. PMID: 19696185
(Source: Diabetes)
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Prada, P. O.; Ropelle, E. R.; Mourao, R. H.; de Souza, C. T.; Pauli, J. R.; Cintra, D. E.; Schenka, A.; Rocco, S. A.; Rittner, R.; Franchini, K. G.; Vassallo, J.; Velloso, L. A.; Carvalheira, J. B.; Saad, M. J. A. Tags: Statement of Retraction Source Type: research
Familial Hypercholesterolemia and Type 2 Diabetes in the Old Order Amish
Alleles associated with lower levels of LDL cholesterol (LDL-C) have recently been associated with an increased risk of type 2 diabetes (T2D), highlighting the complex relationship between LDL-C and diabetes. This observation begs the question of whether LDL-C–raising alleles are associated with a decreased risk of T2D. This issue was recently addressed in a large familial hypercholesterolemia (FH) screening study, which reported a lower prevalence of self-reported diabetes in FH subjects than in age-matched relatives without FH. To extend this observation, we tested the association of FH with diabetes status and gly...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Xu, H.; Ryan, K. A.; Jaworek, T. J.; Southam, L.; Reid, J. G.; Overton, J. D.; Baras, A.; Puurunen, M. K.; Zeggini, E.; Taylor, S. I.; Shuldiner, A. R.; Mitchell, B. D. Tags: Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Dominant ER Stress-Inducing WFS1 Mutations Underlie a Genetic Syndrome of Neonatal/Infancy-Onset Diabetes, Congenital Sensorineural Deafness, and Congenital Cataracts
Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal diabetes have been identified to date. There are still patients with neonatal diabetes who have novel genetic syndromes. We performed exome sequencing in a patient and his unrelated, unaffected parents to identify the genetic etiology of a syndrome characterized by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. We identified 5 patients, ...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: De Franco, E.; Flanagan, S. E.; Yagi, T.; Abreu, D.; Mahadevan, J.; Johnson, M. B.; Jones, G.; Acosta, F.; Mulaudzi, M.; Lek, N.; Oh, V.; Petz, O.; Caswell, R.; Ellard, S.; Urano, F.; Hattersley, A. T. Tags: Islet Biology-Beta Cell-Development and Postnatal Growth Genetics/Genomes/Proteomics/Metabolomics Source Type: research
UBASH3A Mediates Risk for Type 1 Diabetes Through Inhibition of T-Cell Receptor-Induced NF-{kappa}B Signaling
Although over 40 type 1 diabetes (T1D) risk loci have been mapped in humans, the causative genes and variants for T1D are largely unknown. Here, we investigated a candidate gene in the 21q22.3 risk locus—UBASH3A, which is primarily expressed in T cells where it is thought to play a largely redundant role. Genetic variants in UBASH3A have been shown to be associated with several autoimmune diseases in addition to T1D. However, the molecular mechanism underlying these genetic associations is unresolved. Our study reveals a previously unrecognized role of UBASH3A in human T cells: UBASH3A attenuates the NF-B signal tran...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Ge, Y.; Paisie, T. K.; Newman, J. R. B.; McIntyre, L. M.; Concannon, P. Tags: Genetics/Genomes/Proteomics/Metabolomics Source Type: research
A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This v...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Manning, A.; Highland, H. M.; Gasser, J.; Sim, X.; Tukiainen, T.; Fontanillas, P.; Grarup, N.; Rivas, M. A.; Mahajan, A.; Locke, A. E.; Cingolani, P.; Pers, T. H.; Vinuela, A.; Brown, A. A.; Wu, Y.; Flannick, J.; Fuchsberger, C.; Gamazon, E. R.; Gaulton, Tags: Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Neurturin and a GLP-1 Analogue Act Synergistically to Alleviate Diabetes in Zucker Diabetic Fatty Rats
In this study, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a glucagon-like peptide 1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass and prevented deterioration of islet organization. However, unlike liraglutide-treated rats, NRTN-mediated improvements were not associated with reduced body weight or food intake. Acute NRTN treatment did not act...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Trevaskis, J. L.; Sacramento, C. B.; Jouihan, H.; Ali, S.; Le Lay, J.; Oldham, S.; Bhagroo, N.; Boland, B. B.; Cann, J.; Chang, Y.; ODay, T.; Howard, V.; Reers, C.; Winzell, M. S.; Smith, D. M.; Feigh, M.; Barkholt, P.; Schreiter, K.; Austen, M.; Andag, U Tags: Integrated Physiology-Other Hormones Pharmacology and Therapeutics Source Type: research
Empagliflozin and Kinetics of Renal Glucose Transport in Healthy Individuals and Individuals With Type 2 Diabetes
Renal glucose reabsorption was measured with the stepped hyperglycemic clamp in 15 subjects with type 2 diabetes mellitus (T2DM) and 15 without diabetes after 2 days and after more chronic (14 days) treatment with empagliflozin. Patients with T2DM had significantly greater maximal renal glucose transport (TmG) compared with subjects without diabetes at baseline (459 ± 53 vs. 337 ± 25 mg/min; P < 0.05). Empagliflozin treatment for 48 h reduced the TmG in both individuals with and without diabetes by 44 ± 7 and 53 ± 6%, respectively (both P < 0.001). TmG was further reduced by empagliflozin ...
Source: Diabetes - June 21, 2017 Category: Endocrinology Authors: Al-Jobori, H.; Daniele, G.; Cersosimo, E.; Triplitt, C.; Mehta, R.; Norton, L.; DeFronzo, R. A.; Abdul-Ghani, M. Tags: Complications Source Type: research
