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https://www.readbyqxmd.com/read/28912305/effects-of-liraglutide-on-weight-loss-fat-distribution-and-%C3%AE-cell-function-in-obese-subjects-with-prediabetes-or-early-type-2-diabetes
#1
Francesca Santilli, Paola G Simeone, Maria T Guagnano, Marika Leo, Marica T Maccarone, Augusto Di Castelnuovo, Cristina Sborgia, Riccardo C Bonadonna, Ermanno Angelucci, Virginia Federico, Stefano Cianfarani, Lamberto Manzoli, Giovanni Davì, Armando Tartaro, Agostino Consoli
OBJECTIVE: Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes...
September 14, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28895642/initiation-of-basal-insulin-analog-treatment-for-type-2-diabetes-and-reasons-behind-patients-treatment-persistence-behavior-real-world-data-from-germany
#2
Elisabeth Moennig, Magaly Perez-Nieves, Irene Hadjiyianni, Dachuang Cao, Jasmina Ivanova, Ralf Klask
Background Poor treatment persistence can affect the real-world effectiveness of insulin therapy. A cross-sectional online survey in 942 patients with type 2 diabetes from 7 different countries evaluated patient experience when initiating basal insulin and the reasons behind insulin persistence patterns. Here, we report the quantitative results for the subset of patients from Germany. Methods Adults with type 2 diabetes who had initiated basal insulin during the last 3-24 months, identified from market-research panels, participated in the survey...
September 11, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28889219/a-validated-uplc-ms-ms-method-coupled-with-protein-precipitation-and-ion-exchange-solid-phase-extraction-for-the-quantitation-of-porcine-relaxin-b29-in-dog-plasma-and-its-application-to-a-pharmacokinetic-study
#3
Chong Su, Hui Sun, Hong Yang, Lei Yin, Jiwen Zhang, John Paul Fawcett, Jingkai Gu
Porcine relaxin is a 6 kDa peptide hormone of pregnancy with important physiological and pharmacological effects. It contains a number of analogs of which porcine relaxin B29 is one of the most important. To support the development of porcine relaxin B29 as a new drug, we established an UPLC-MS/MS method for its quantitation in dog plasma. Sample preparation by protein precipitation and ion exchange solid phase extraction was followed by UPLC on an XBridge™ BEH300 C18 column at 40 °C in a run time of only 5...
September 9, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28887047/peptides-from-frog-skin-with-potential-for-development-into-agents-for-type-2-diabetes-therapy
#4
J Michael Conlon, Milena Mechkarska, Yasser H Abdel-Wahab, Peter R Flatt
Several frog skin peptides, first identified as result of their antimicrobial or immunomodulatory activities, have subsequently been shown to stimulate insulin release both in vitro and in vivo and so show potential for development into incretin-based drugs for treatment of patients with Type 2 diabetes mellitus. However, their therapeutic potential as anti-diabetic agents is not confined to this activity as certain frog skin-derived peptides, such as magainin-AM2 and CPF-SE1 and analogs of hymenochirin-1B, tigerinin-1R, and esculentin-2CHa, have been shown to increase insulin sensitivity, promote β-cell proliferation, suppress pancreatic and circulating glucagon concentrations, improve the lipid profile, and selectively alter expression of genes involved in insulin secretion and action in mice with diet-induced obesity, insulin resistance and impaired glucose tolerance...
September 5, 2017: Peptides
https://www.readbyqxmd.com/read/28874536/microrna-277-targets-insulin-like-peptides-7-and-8-to-control-lipid-metabolism-and-reproduction-in-aedes-aegypti-mosquitoes
#5
Lin Ling, Vladimir A Kokoza, Changyu Zhang, Emre Aksoy, Alexander S Raikhel
Hematophagous female mosquitoes transmit numerous devastating human diseases, including malaria, dengue fever, Zika virus, and others. Because of their obligatory requirement of a vertebrate blood meal for reproduction, these mosquitoes need a lot of energy; therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. Lipids are the major energy store providing the fuel required for host seeking and reproduction. They are essential components of the fat body, a metabolic tissue that is the insect analog of vertebrate liver and adipose tissue...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28874187/prolonged-preoperative-treatment-of-acromegaly-with-somatostatin-analogs-may-improve-surgical-outcome-in-patients-with-invasive-pituitary-macroadenoma-knosp-grades-1-3-a-retrospective-cohort-study-conducted-at-a-single-center
#6
Lian Duan, Huijuan Zhu, Bing Xing, Feng Gu
BACKGROUND: This study aimed to investigate preoperative somatostatin analogs (SSAs) treatment on the surgical outcome in patients with acromegaly. METHODS: An analysis of 358 patients with acromegaly was conducted. The preoperative medical therapy group (81 patients) received SSA treatment for at least 3 months prior to surgery, while the primary surgery group (277 patients) underwent transsphenoidal surgery directly. Follow-up duration was ≥3 months. Tumor invasion was evaluated by magnetic resonance imaging (MRI) and classified according to the Knosp grading system...
September 6, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28867301/nonalcoholic-fatty-liver-disease-as-a-nexus-of-metabolic-and-hepatic-diseases
#7
REVIEW
Varman T Samuel, Gerald I Shulman
NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available...
August 29, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28846865/insulin-glargine-and-its-two-active-metabolites-a-sensitive-16pm-and-robust-simultaneous-hybrid-assay-coupling-immunoaffinity-purification-with-lc-ms-ms-to-support-biosimilar-clinical-studies
#8
Yang Xu, Li Sun, Melanie Anderson, Philippe Bélanger, Vincent Trinh, Patricia Lavallée, Bhavna Kantesaria, Marie-Josée Marcoux, Sheila Breidinger, Kevin P Bateman, Dina Goykhman, Eric J Woolf
MK-1293 is a newly approved follow-on/biosimilar insulin glargine for the treatment of Type 1 and Type 2 diabetics. To support pivotal clinical studies during biosimilar evaluation, a sensitive, specific and robust liquid chromatography and tandem mass spectrometry (LC-MS/MS) assay for the simultaneous quantification of glargine and its two active metabolites, M1 and M2 were developed. Strategies to overcome analytical challenges, so as to optimize assay sensitivity and improve ruggedness, were evolved, resulting in a fully validated LC-MS/MS method with a lower limit of quantification (LLOQ) at 0...
August 19, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28837922/development-of-glut4-selective-antagonists-for-multiple-myeloma-therapy
#9
Changyong Wei, Richa Bajpai, Horrick Sharma, Monique Heitmeier, Atul D Jain, Shannon M Matulis, Ajay K Nooka, Rama K Mishra, Paul W Hruz, Gary E Schiltz, Mala Shanmugam
Cancer cells consume more glucose to fuel metabolic programs fundamental to sustaining their survival, growth and proliferation. Among the fourteen SLC2A family members, GLUTs 1 and 4 are high-affinity glucose transporters. GLUT4 (SLC2A4) is highly expressed in muscle and adipose tissue. Basally retained within the cell, GLUT4 traffics to the plasma membrane (PM) in response to insulin and exercise-stimulation. The plasma cell malignancy multiple myeloma (MM) exhibits increased constitutive expression of GLUT4 on the PM, co-opting use of GLUT4 for survival and proliferation...
October 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28835593/pitfalls-in-early-biochemical-evaluation-after-transsphenoidal-surgery-in-patients-with-acromegaly
#10
Hiroshi Nishioka, Noriaki Fukuhara, Mitsuo Yamaguchi-Okada, Akira Takeshita, Yasuhiro Takeuchi, Shozo Yamada
Although the current remission criteria for acromegaly are clear and concise, some pitfalls have been reported in early endocrinological evaluation after surgery. To evaluate the long-term (>4 year) outcome and to detect the pitfalls in early evaluation, we retrospectively reviewed 128 patients with acromegaly who underwent primary transsphenoidal surgery during 2011 and 2012. These included 66 men and 62 women, aged from 7 to 76 (mean 46) years old. 49 patients (38.3%) were preoperatively treated with somatostatin analog (SSA)...
August 23, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28830317/growth-hormone-secretagogue-treatment-in-hypogonadal-men-raises-serum-insulin-like-growth-factor-1-levels
#11
John T Sigalos, Alexander W Pastuszak, Andrew Allison, Samuel J Ohlander, Amin Herati, Mark C Lindgren, Larry I Lipshultz
Realizing the reported misuse of human growth hormone (GH), investigation of a safe alternative mechanism for increasing endogenous GH is needed. Several GH secretagogues are available, including GH-releasing peptides (GHRPs) GHRP-2 and GHRP-6, and the GH-releasing hormone analog, sermorelin (SERM). Insulin-like growth factor 1 (IGF-1) serves as a surrogate marker for GH. Here, the effect of GHRP/SERM therapy on IGF-1 levels is evaluated. A retrospective review of medical records was performed for 105 men on testosterone (T) therapy seeking increases in lean body mass and fat loss who were prescribed 100 mcg of GHRP-6, GHRP-2, and SERM three times daily...
August 1, 2017: American Journal of Men's Health
https://www.readbyqxmd.com/read/28825668/changes-in-stress-and-appetite-responses-in-male-power-trained-athletes-during-intensive-training-camp
#12
Satomi Oshima, Chisato Takehata, Ikuko Sasahara, Eunjae Lee, Takao Akama, Motoko Taguchi
An intensive consecutive high-volume training camp may induce appetite loss in athletes. Therefore, this study aimed to investigate the changes in stress and appetite responses in male power-trained athletes during an intensive training camp. The measurements at Day 2 and at the end of a 9-day intensive training camp (Camp1 and Camp2, respectively) were compared with those of the resting period (Rest) and the regular training period (Regular; n = 13). The stress state was assessed based on plasma cortisol level, salivary immunoglobulin A level, and a profile of mood states score...
August 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28822091/effect-of-ap102-a-subtype-2-and-5-specific-somatostatin-analog-on-glucose-metabolism-in-rats
#13
Erika Tarasco, Petra Seebeck, Svende Pfundstein, Adrian F Daly, Philippe J Eugster, Alan G Harris, Eric Grouzmann, Thomas A Lutz, Christina N Boyle
PURPOSE: Somatostatin analogs are widely used to treat conditions associated with hormonal hypersecretion such as acromegaly and metastatic neuroendocrine tumors. First generation somatostatin analogs, such as octreotide and lanreotide, have high affinity for somatostatin receptor subtype 2 (SSTR2), but have incomplete efficacy in many patients. Pasireotide targets multiple SSTRs, having the highest affinity for SSTR5, but causes hyperglycemia and diabetes mellitus in preclinical and clinical studies...
August 18, 2017: Endocrine
https://www.readbyqxmd.com/read/28820912/impact-of-novel-palmitoylated-prolactin-releasing-peptide-analogs-on-metabolic-changes-in-mice-with-diet-induced-obesity
#14
Veronika Pražienková, Martina Holubová, Helena Pelantová, Martina Bugáňová, Zdenko Pirník, Barbora Mikulášková, Andrea Popelová, Miroslava Blechová, Martin Haluzík, Blanka Železná, Marek Kuzma, Jaroslav Kuneš, Lenka Maletínská
Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus...
2017: PloS One
https://www.readbyqxmd.com/read/28798723/structural-perspectives-of-insulin-receptor-isoform-selective-insulin-analogs
#15
Jiří Jiráček, Lenka Žáková
A significant drawback of the exogenous administration of insulin to diabetics is the non-physiological profile of insulin action resulting in the insufficient suppression of hepatic glucose production, which is the main contributing factor to diabetic hyperglycemia under fasting conditions and the basis of the challenge to restore a more physiological glucose profile in diabetes. The insulin receptor (IR) exists in two alternatively spliced variants, IR-A and IR-B, with different tissue distribution. While peripheral tissues contain different proportions of both isoforms, hepatic cells almost exclusively contain IR-B...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28796787/the-quinic-acid-derivative-kz-41-prevents-glucose-induced-caspase-3-activation-in-retinal-endothelial-cells-through-an-igf-1-receptor-dependent-mechanism
#16
Hui He, Rebecca L Weir, Jordan J Toutounchian, Jayaprakash Pagadala, Jena J Steinle, Jerome Baudry, Duane D Miller, Charles R Yates
Retinal microaneurysms, an early disease manifestation of diabetic retinopathy, are associated with retinal endothelial cell (REC) death and macular edema. We previously demonstrated that a quinic acid (QA) analog, KZ-41, promoted REC survival by blunting stress-induced p38 MAPK activation. Herein, we sought to expand our understanding of the pro-survival signal transduction pathways actuated by KZ-41. Using human RECs exposed to high glucose (25 mM, 72 hours), we demonstrated that KZ-41 blocks caspase-3 activation by triggering phosphorylation of the PI3K regulatory subunit (p85; Tyr458) and its downstream target Akt (Ser473)...
2017: PloS One
https://www.readbyqxmd.com/read/28792170/consensus-on-basal-insulin-in-the-management-of-type-2-diabetes-which-when-and-how
#17
Samit Ghosal, Binayak Sinha, Anirban Majumder, Ashok Kumar Das, Awadhesh Kumar Singh, Biswajit Ghoshdastidar, Debasish Maji, Ghanshyam Goyal, Jagat Jyoti Mukherjee, Kalyan Kumar Gangopadhyay, Mathew John, Sanjay Chatterjee, Shalini Jaggi, Subir Ray, Sujoy Majumdar, Surendra Kumar Sharma
INTRODUCTION: Type 2 diabetes mellitus (T2DM) has attained epidemic proportions and continues to increase despite the availability of a number of oral antidiabetic medications and major advances made in insulin delivery since its discovery nearly a hundred years ago. One, amongst many other reasons responsible for the inability to achieve adequate glycaemic control in a substantial proportion of T2DM patients is the delayed initiation and inappropriate intensification of insulin treatment...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28780057/top-down-mass-spectrometric-immunoassay-for-human-insulin-and-its-therapeutic-analogs
#18
Dobrin Nedelkov, Eric E Niederkofler, Paul E Oran, Scott Peterman, Randall W Nelson
Measurement of insulin and its therapeutic analogs is important in diabetes, hypoglycemia, sports anti-doping and toxicology. Commercial insulin immunoassays fail to detect commonly prescribed insulin analogs. Because of their unique sequences and masses, these analogs are readily measured and distinguished with mass spectrometric (MS) assays. Reviewed here is an insulin mass spectrometric immunoassay (MSIA) that combines micro-scale immunoaffinity capture with sensitive MS detection of insulin and its therapeutic analogs...
August 3, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28771323/synthetic-advances-in-insulin-like-peptides-enable-novel-bioactivity
#19
Fa Liu, Pengyun Li, Vasily Gelfanov, John Mayer, Richard DiMarchi
Insulin is a miraculous hormone that has served a seminal role in the treatment of insulin-dependent diabetes for nearly a century. Insulin resides within in a superfamily of structurally related peptides that are distinguished by three invariant disulfide bonds that anchor the three-dimensional conformation of the hormone. The additional family members include the insulin-like growth factors (IGF) and the relaxin-related set of peptides that includes the so-called insulin-like peptides. Advances in peptide chemistry and rDNA-based synthesis have enabled the preparation of multiple insulin analogues...
August 3, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28770459/effect-of-liraglutide-on-myocardial-glucose-uptake-and-blood-flow-in-stable-chronic-heart-failure-patients-a-double-blind-randomized-placebo-controlled-live-sub-study
#20
Roni Nielsen, Anders Jorsal, Peter Iversen, Lars Poulsen Tolbod, Kirsten Bouchelouche, Jens Sørensen, Hendrik Johannes Harms, Allan Flyvbjerg, Lise Tarnow, Caroline Kistorp, Ida Gustafsson, Hans Erik Bøtker, Henrik Wiggers
BACKGROUND: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). METHODS AND RESULTS: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design...
August 2, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
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