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https://www.readbyqxmd.com/read/28726377/a-novel-targeted-mass-spectrometry-approach-enabled-discov-ery-of-o-glycosylated-insulin-and-related-signaling-peptides-in-mouse-and-human-pancreatic-islets
#1
Qing Yu, Alejandra Canales, Matthew S Glover, Rahul Das, Xudong Shi, Yang Liu, Mark P Keller, Alan D Attie, Lingjun Li
O-linked glycosylation often involves the covalent attachment of sugar moieties to the hydroxyl group of serine or threonine on proteins/peptides. Despite growing interest in glycoproteins, little attention has been directed to glycosylated signaling peptides, largely due to lack of enabling analytical tools. Here we explore the occurrence of naturally O-linked glycosylation on the signaling peptides extracted from mouse and human pancreatic islets using mass spectrometry (MS). A novel targeted MS-based method is developed to increase the likelihood of capturing these modified signaling peptides and to provide improved sequence coverage and accurate glycosite localization, enabling the first large-scale discovery of O-glycosylation on signaling peptides...
July 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28721081/insulin-glargine-300-u-ml-for-basal-insulin-therapy-in-type-1-and-type-2-diabetes-mellitus
#2
REVIEW
Ip Tim Lau, Ka Fai Lee, Wing Yee So, Kathryn Tan, Vincent Tok Fai Yeung
OBJECTIVE: To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM). MATERIALS AND METHODS: Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. RESULTS: In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28721067/phase-i-dose-escalation-study-of-long-acting-pasireotide-in-patients-with-neuroendocrine-tumors
#3
James C Yao, Jennifer A Chan, Alain C Mita, Madan G Kundu, Karina Hermosillo Reséndiz, Ke Hu, Shoba Ravichandran, Jonathan R Strosberg, Edward M Wolin
This phase I study aimed at determining the maximum tolerated dose (MTD) and characterizing the safety, tolerability, pharmacokinetics (PKs), and efficacy of pasireotide in patients with advanced neuroendocrine tumors (NETs). Patients were enrolled in two phases: dose-escalation phase (to determine the MTD) at a starting dose of 80 mg pasireotide long-acting release (LAR) i.m. followed by a dose-expansion phase (to evaluate safety and prelimi-nary efficacy). Associations between PK/pharmacodynamic parameters and clinical outcomes were evaluated using linear regression analysis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28720583/central-effects-of-insulin-detemir-on-feeding-body-weight-and-metabolism-in-rats
#4
Joseph R Vasselli, F Xavier Pi-Sunyer, Daniel G Wall, Catherine S John, Colin D Chapman, Paul J Currie
Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the CNS. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE) and respiratory quotient (RQ). Also in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE and RQ when microinjected directly into the paraventricular nucleus (PVN)...
July 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28704103/postprandial-dosing-of-bolus-insulin-in-patients-with-type-1-diabetes-a-cross-sectional-study-using-data-from-the-t1d-exchange-registry
#5
Anne Peters, Michelle A Van Name, Brian Larsen Thorsted, Johanne Spanggaard Piltoft, William V Tamborlane
OBJECTIVE: To assess the prevalence and characteristics of patients with type 1 diabetes who dose bolus insulin postprandial (PostP) versus preprandial (PreP). METHODS: Data for this cross-sectional study were obtained from 21,533 participants in the T1D Exchange registry. Data were drawn from the enrollment questionnaire. Patients who dosed 'immediately before meal' or 'several minutes before meal' were classified as PreP. Patients who dosed 'during meal' or 'after meal' were classified as PostP...
July 13, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28702259/clinical-effects-cardiovascular-and-renal-outcomes-associated-with-rapid-acting-insulin-analogs-among-individuals-with-type-2-diabetes-a-nation-wide-observational-cohort-study
#6
Ann-Marie Svensson, Mervete Miftaraj, Stefan Franzén, Björn Eliasson
BACKGROUND: Rapid-acting insulin analogs (RAIs) have not been examined for long-term safety in randomized clinical trials. We performed a nationwide longitudinal cohort study among individuals with type 2 diabetes (T2DM) to address cardiovascular safety and mortality among users of lispro, aspart and glulisine insulins. METHODS: We used four national registers, following patients previously not treated with RAI but with continuous use of RAIs in 2005-2014 up to 6...
2017: Clinical Diabetes and Endocrinology
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-anti-obesity-effects-in-diet-induced-obese-mice
#7
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
Glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans in addition to their potent anti-diabetic effects. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their anti-obesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog, exenatide, for the development of promising new anti-obesity drugs...
July 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28688245/the-timing-of-administration-of-exogenous-glucocorticoid-affects-24hour-growth-hormone-secretion-in-children
#8
Ole D Wolthers, Nilani Ramshanker, Carsten Heuck, Jan Frystyk
Exogenous glucocorticoids may suppress linear growth by affecting the diurnal secretory rhythm of GH. OBJECTIVE: To assess whether the timing of exogenous glucocorticoid administration affects GH secretion in children. DESIGN: Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-period cross-over trial, with a 1-day un-in, and two 4-day periods of 5mg prednisolone in the morning or in the evening, respectively, separated by a 3-week washout period...
July 1, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28687614/signal-integration-at-the-pi3k-p85-xbp1-hub-endows-coagulation-protease-activated-protein-c-with-insulin-like-function
#9
Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J Müller, Charles T Esmon, Peter P Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling both impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER)-homeostasis. Analogous to insulin, physiological levels of aPC maintain endoplasmic reticulum (ER) proteostasis in DKD...
July 7, 2017: Blood
https://www.readbyqxmd.com/read/28686504/prolactin-and-oleic-acid-synergistically-stimulate-%C3%AE-cell-proliferation-and-growth-in-rat-islets
#10
Todd Clark Brelje, Nicholas V Bhagroo, Laurence E Stout, Robert L Sorenson
Islet adaptation to pregnancy is largely influenced by prolactin and placental lactogens. In addition serum lipids are significantly increased. Here, we report the novel observation that prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth. In neonatal rat islets, prolactin increased proliferation 6-fold, oleic acid 3.5-fold, and their combination 15-fold. The expression of insulin in these dividing cells establishes them as β-cells. Similar changes were seen in islet growth...
July 4, 2017: Islets
https://www.readbyqxmd.com/read/28685509/stepwise-approach-to-problematic-hypoglycemia-in-korea-educational-technological-and-transplant-interventions
#11
REVIEW
Sang Man Jin
Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring...
June 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28683239/comparison-of-efficacy-and-safety-of-glargine-and-detemir-insulin-in-the-management-of-inpatient-hyperglycemia-and-diabetes
#12
Rodolfo J Galindo, Georgia M Davis, Maya Fayfman, David Reyes-Umpierrez, David Alfa, Limin Peng, Ronald Tamler, Francisco J Pasquel, Guillermo E Umpierrez
OBJECTIVE: Glargine and detemir insulin are the two most commonly prescribed basal insulin analogs for the ambulatory and inpatient management of diabetes. The efficacy and safety of basal insulin analogs in the hospital setting has not been established. METHODS: This observational study compared differences in glycemic control and outcomes in non-ICU patients with blood glucose (BG) >140 mg/dl who were treated with glargine or detemir, between 01/01/2012 and 09/30/2015 in two academic centers...
July 6, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28679626/the-bradykinin-bk-cgmp-pkg-pathway-augments-insulin-sensitivity-via-upregulation-of-mapk-phosphatase-5-and-inhibition-of-jun-kinase-jnk
#13
Maria E Frigolet, Garry Thomas, Kristin Beard, Huogen Lu, Lijiang Liu, I George Fantus
Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase (eNOS), nitric oxide (NO) generation, and decreased activity of the mitogen activated protein kinase (MAPK), JNK (c-Jun-N-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity which in turn, activates protein kinase G (PKG) by increasing cGMP levels...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28668719/evaluation-of-the-timing-and-coordination-of-prandial-insulin-administration-in-the-hospital
#14
Dhuha Alwan, Esther Chipps, Po-Yin Yen, Kathleen Dungan
AIMS: The objective of this study was to examine the relationship between measures of coordinated insulin delivery and capillary blood glucose (CBG) levels among hospitalized patients and to assess nurse perceptions of insulin administration. METHODS: Hospitalized patients (n=451) receiving rapid acting insulin analog (RAIA) using carbohydrate counting were retrospectively analyzed. Nurses (n=35) were asked to complete an 18-item anonymous survey assessing perception of RAIA dosing...
June 22, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28652541/development-of-ghrelin-transgenic-mice-for-elucidation-of-clinical-implication-of-ghrelin
#15
Daisuke Aotani, Hiroyuki Ariyasu, Satoko Shimazu-Kuwahara, Yoshiyuki Shimizu, Hidenari Nomura, Yoshiteru Murofushi, Kentaro Kaneko, Ryota Izumi, Masaki Matsubara, Hajime Kanda, Michio Noguchi, Tomohiro Tanaka, Toru Kusakabe, Takashi Miyazawa, Kazuwa Nakao
To elucidate the clinical implication of ghrelin, we have been trying to generate variable models of transgenic (Tg) mice overexpressing ghrelin. We generated Tg mice overexpressing des-acyl ghrelin in a wide variety of tissues under the control of β-actin promoter. While plasma des-acyl ghrelin level in the Tg mice was 44-fold greater than that of control mice, there was no differences in the plasma ghrelin level between des-acyl ghrelin Tg and the control mice. The des-acyl ghrelin Tg mice exhibited the lower body weight and the shorter body length due to modulation of GH-IGF-1 axis...
2017: Endocrine Journal
https://www.readbyqxmd.com/read/28648676/regulation-of-glut4-activity-in-myotubes-by-3-o-methyl-d-glucose
#16
Ofer Shamni, Guy Cohen, Arie Gruzman, Hilal Zaid, Amira Klip, Erol Cerasi, Shlomo Sasson
The rate of glucose influx to skeletal muscles is determined primarily by the number of functional units of glucose transporter-4 (GLUT4) in the myotube plasma membrane. The abundance of GLUT4 in the plasma membrane is tightly regulated by insulin or contractile activity, which employ distinct pathways to translocate GLUT4-rich vesicles from intracellular compartments. Various studies have indicated that GLUT4 intrinsic activity is also regulated by conformational changes and/or interactions with membrane components and intracellular proteins in the vicinity of the plasma membrane...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#17
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28609372/pancreatic-polypeptide-cell-proliferation-in-the-pancreas-and-duodenum-coexisting-in-a-patient-with-pancreatic-adenocarcinoma-treated-with-a-glp-1-analog
#18
Geoffrey A Talmon, J David Wren, Christophe L Nguyen, Parviz M Pour
A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28590908/biomimetic-insulin-imprinted-polymer-nanoparticles-as-a-potential-oral-drug-delivery-system
#19
Pijush Kumar Paul, Alongkot Treetong, Roongnapa Suedee
In this study, we investigate molecularly imprinted polymers (MIPs), which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7...
June 27, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28577277/in-vitro-production-of-insulin-responsive-skeletal-muscle-tissue-from-mouse-embryonic-stem-cells-by-spermine-induced-differentiation-method
#20
Mikako Saito, Ayano Ishida, Shota Nakagawa
The treatment of an embryoid body with spermine for a short duration can trigger the generation of a 3-dimensional multilayer myotube sheet (MMTS) that shows pulsatile activity. MMTS was previously characterized as a model of skeletal muscle tissue. In the present work, the insulin responsiveness of MMTS was investigated because it is an essential function for a model of skeletal muscle. The glucose uptake activity of MMTS was analyzed by confocal microscopy using fluorescent glucose analogs, namely 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) and its L-glucose counterpart, 2-NBDLG...
July 2017: Human Cell
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