The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor
This study examined the ability of GIP(3–30)NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism in humans. Eight lean subjects were studied by measuring arteriovenous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of GIP, GIP(3–30)NH2, or both GIP and GIP(3–30)NH2. During infusion of GIP(3–30)NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were l...
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Asmar, M.; Asmar, A.; Simonsen, L.; Gasbjerg, L. S.; Sparre-Ulrich, A. H.; Rosenkilde, M. M.; Hartmann, B.; Dela, F.; Holst, J. J.; Bülow, J. Tags: Integrated Physiology-Other Hormones Metabolism Source Type: research
Pivotal Role of O-GlcNAc Modification in Cold-Induced Thermogenesis by Brown Adipose Tissue Through Mitochondrial Biogenesis
In conclusion, O-GlcNAc modification is essential for cold-induced thermogenesis and mitochondrial biogenesis in BAT. Glucose flux into BAT may be a signal to maintain BAT physiological responses. (Source: Diabetes)
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Ohashi, N.; Morino, K.; Ida, S.; Sekine, O.; Lemecha, M.; Kume, S.; Park, S.-Y.; Choi, C. S.; Ugi, S.; Maegawa, H. Tags: Insulin Action-Cellular and Molecular Metabolism Source Type: research
Dual Regulation of Gluconeogenesis by Insulin and Glucose in the Proximal Tubules of the Kidney
In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium–glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. In contrast, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor. In the HK-2 cells, the gluconeogeni...
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Sasaki, M.; Sasako, T.; Kubota, N.; Sakurai, Y.; Takamoto, I.; Kubota, T.; Inagi, R.; Seki, G.; Goto, M.; Ueki, K.; Nangaku, M.; Jomori, T.; Kadowaki, T. Tags: Insulin Action-Cellular and Molecular Metabolism Source Type: research
The SNARE Protein Syntaxin-1a Plays an Essential Role in Biphasic Exocytosis of the Incretin Hormone Glucagon-Like Peptide 1
Exocytosis of the hormone glucagon-like peptide 1 (GLP-1) by the intestinal L cell is essential for the incretin effect after nutrient ingestion and is critical for the actions of dipeptidyl peptidase 4 inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. Two-photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a first peak at 1–6 min and a second peak at 7–12 min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules under basal and stimula...
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Wheeler, S. E.; Stacey, H. M.; Nahaei, Y.; Hale, S. J.; Hardy, A. B.; Reimann, F.; Gribble, F. M.; Larraufie, P.; Gaisano, H. Y.; Brubaker, P. L. Tags: Metabolism Source Type: research
In This Issue of Diabetes
(Source: Diabetes)
Source: Diabetes - August 22, 2017 Category: Endocrinology Tags: In This Issue Source Type: research
Response to Comment on Rodriguez-Calvo et al. Increase in Pancreatic Proinsulin and Preservation of {beta}-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset. Diabetes 2017;66:1334-1345
(Source: Diabetes)
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Rodriguez-Calvo, T.; Atkinson, M.; von Herrath, M. G. Tags: Immunology e-Letters: Comments and Responses Source Type: research
Comment on Rodriguez-Calvo et al. Increase in Pancreatic Proinsulin and Preservation of {beta}-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset. Diabetes 2017;66:1334-1345
(Source: Diabetes)
Source: Diabetes - August 22, 2017 Category: Endocrinology Authors: Skog, O.; Korsgren, O. Tags: Immunology e-Letters: Comments and Responses Source Type: research
Issues and Events
(Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Tags: Issues and Events Source Type: research
Recessively Inherited LRBA Mutations Cause Autoimmunity Presenting as Neonatal Diabetes
Young-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition, but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients’ prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM) (diagnosis <6 months). We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA. Biallelic LRBA mutations cause common vari...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Johnson, M. B.; De Franco, E.; Lango Allen, H.; Al Senani, A.; Elbarbary, N.; Siklar, Z.; Berberoglu, M.; Imane, Z.; Haghighi, A.; Razavi, Z.; Ullah, I.; Alyaarubi, S.; Gardner, D.; Ellard, S.; Hattersley, A. T.; Flanagan, S. E. Tags: Genetics-Type 1 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Genetic Variation at the Sulfonylurea Receptor, Type 2 Diabetes, and Coronary Heart Disease
Despite widespread clinical use in the treatment of type 2 diabetes, the impact of sulfonylurea therapy on cardiovascular outcomes remains uncertain. Studies of naturally occurring genetic variation can be used to anticipate the expected clinical consequences of a pharmacological therapy. A common missense variant in the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S) promotes closure of the target channel of sulfonylurea therapy and is associated with increased insulin secretion, thus mimicking the effects of sulfonylurea therapy. Using individual-level data from 120,286 participants in the UK Biob...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Emdin, C. A.; Klarin, D.; Natarajan, P.; CARDIOGRAM Exome Consortium; Florez, J. C.; Kathiresan, S.; Khera, A. V. Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants
Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci. Thirty type 2 diabetes or fasting glucose–raising alleles were associated with a measure of first-phase i...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Wood, A. R.; Jonsson, A.; Jackson, A. U.; Wang, N.; van Leewen, N.; Palmer, N. D.; Kobes, S.; Deelen, J.; Boquete-Vilarino, L.; Paananen, J.; Stancakova, A.; Boomsma, D. I.; de Geus, E. J. C.; Eekhoff, E. M. W.; Fritsche, A.; Kramer, M.; Nijpels, G.; Simo Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated With Reduced Energy Expenditure in American Indians
Pima Indians living in Arizona have a high prevalence of obesity, and we have previously shown that a relatively lower energy expenditure (EE) predicts weight and fat mass gain in this population. EE is a familial trait (heritability = 0.52); therefore, in the current study, we aimed to identify genetic variants that affect EE and thereby influence BMI and body fatness in Pima Indians. Genotypic data from 491,265 variants were analyzed for association with resting metabolic rate (RMR) and 24-h EE assessed in a whole-room calorimeter in 507 and 419 Pima Indians, respectively. Variants associated with both measures of EE wer...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Piaggi, P.; Masindova, I.; Muller, Y. L.; Mercader, J.; Wiessner, G. B.; Chen, P.; SIGMA Type 2 Diabetes Consortium; Kobes, S.; Hsueh, W.-C.; Mongalo, M.; Knowler, W. C.; Krakoff, J.; Hanson, R. L.; Bogardus, C.; Baier, L. J. Tags: Obesity-Human Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Higher Plasma Methylglyoxal Levels Are Associated With Incident Cardiovascular Disease in Individuals With Type 1 Diabetes: A 12-Year Follow-up Study
This study shows for the first time in our knowledge that plasma MGO levels are associated with cardiovascular events in individuals with type 1 diabetes. MGO may explain, at least in part, the increased risk for CVD in type 1 diabetes. (Source: Diabetes)
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Hanssen, N. M. J.; Scheijen, J. L. J. M.; Jorsal, A.; Parving, H.-H.; Tarnow, L.; Rossing, P.; Stehouwer, C. D. A.; Schalkwijk, C. G. Tags: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes Source Type: research
Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis
The let-7 miRNA family plays a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation and endothelial cell (EC) dysfunction are critical in the pathogenesis of atherosclerosis, including in the setting of diabetes. Here we report that let-7 levels are decreased in diabetic human carotid plaques and in a model of diabetes-associated atherosclerosis, the diabetic ApoE–/– mouse. In vitro platelet-derived growth factor (PDGF)– and tumor necrosis factor-α (TNF-α)–induced vascular SMC and EC activation was associated with reduced let-7 miRNA expression v...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Brennan, E.; Wang, B.; McClelland, A.; Mohan, M.; Marai, M.; Beuscart, O.; Derouiche, S.; Gray, S.; Pickering, R.; Tikellis, C.; de Gaetano, M.; Barry, M.; Belton, O.; Ali-Shah, S. T.; Guiry, P.; Jandeleit-Dahm, K. A. M.; Cooper, M. E.; Godson, C.; Kantha Tags: Complications-Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes Source Type: research
Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism
In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing ...
Source: Diabetes - July 21, 2017 Category: Endocrinology Authors: Hamed, S.; Ullmann, Y.; Egozi, D.; Keren, A.; Daod, E.; Anis, O.; Kabha, H.; Belokopytov, M.; Ashkar, M.; Shofti, R.; Zaretsky, A.; Schlesinger, M.; Teot, L.; Liu, P. Y. Tags: Complications Source Type: research
