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https://www.readbyqxmd.com/read/28724168/efficacy-and-safety-of-glp-1-receptor-agonists-across-the-spectrum-of-type-2-diabetes-mellitus
#1
Lawrence A Leiter, Michael A Nauck
For patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA1c with GLP-1RAs ranged from -1.9 to -0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from -4.0 to -0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway...
July 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28722834/effects-of-gip-glp-1-and-glp-1ras-on-bone-cell-metabolism
#2
Morten S S Hansen, Michaela Terencova, Jacob Frølich, Moustapha Kassem, Morten Frost
The relationship between gut and skeleton is increasingly recognised as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged...
July 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28721686/rationale-for-initiation-and-titration-of-the-basal-insulin-glp-1ra-fixed-ratio-combination-products-ideglira-and-iglarlixi-for-the-management-of-type-2-diabetes
#3
REVIEW
Virginia Valentine, Jennifer Goldman, Jay H Shubrook
Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28721339/the-role-of-glucagon-like-peptide-1-receptor-agonists-in-the-treatment-of-type-2-diabetes
#4
Erin St Onge, Shannon Miller, Elizabeth Clements, Lindsay Celauro, Ke'la Barnes
The role of GLP-1 agonists in the treatment of type 2 diabetes have been shown to be viable options for add-on therapy in diabetic patients, as well as potential monotherapy options. With six available GLP-1 agents, and new combination products in the pipeline, they are a promising drug class for type 2 diabetic patients, especially due to their extended dosing interval and potential weight loss benefits.
June 2017: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28721305/fully-automated-gmp-production-of-68-ga-ga-do3a-vs-cys-40-exendin-4-for-clinical-use
#5
Irina Velikyan, Ulrika Rosenstrom, Olof Eriksson
[(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4/PET-CT targeting glucagon like peptide-1 receptor (GLP-1R) has previously demonstrated its potential clinical value for the detection of insulinomas. The production and accessibility of this radiopharmaceutical is one of the critical factors in realization of clinical trials and routine clinical examinations. Previously, the radiopharmaceutical was prepared manually, however larger scale of clinical trials and healthcare requires automation of the production process in order to limit the operator radiation dose as well as improve tracer manufacturing robustness and on-line documentation for enhanced good manufacturing practice (GMP) compliance...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28721055/chitosan-oligosaccharide-improves-the-therapeutic-efficacy-of-sitagliptin-for-the-therapy-of-chinese-elderly-patients-with-type-2-diabetes-mellitus
#6
Lijie Zhao, Tingli Sun, Lina Wang
Sitagliptin improves glycemic control in type 2 diabetes mellitus (T2DM) patients but its side effects are undesirable. Chitosan oligosaccharide (COS) is expected to improve the therapeutic result as a natural product. A total of 200 elderly T2DM patients were evenly assigned into four groups: sitagliptin group (SG), receiving sitagliptin 100 mg/day; COS group (CG), receiving COS 100 mg/day; combination therapy of sitagliptin and COS group (SCG), receiving both sitagliptin and COS 100 mg/day; and placebo group (PG), receiving placebo 100 mg/day...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#7
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#8
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28714135/yap-suppresses-gluconeogenic-gene-expression-via-pgc1%C3%AE
#9
Yue Hu, Dong-Ju Shin, Hui Pan, Zhiqiang Lin, Jonathan M Dreyfuss, Fernando D Camargo, Ji Miao, Sudha B Biddinger
Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step towards understanding development, regeneration and cancer. The transcriptional regulator Yes-associated protein 1 (YAP) is a key regulator of liver size, development and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28713911/glucagon-like-peptide-1-analogue-liraglutide-ameliorates-atherogenesis-via-inhibiting-advanced-glycation-end-product-induced-receptor-for-advanced-glycosylation-end-product-expression-in-apolipoprotein-e-deficient-mice
#10
Peicheng Li, Zhaosheng Tang, Lin Wang, Bo Feng
Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10 weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713266/significance-of-microbiota-in-obesity-and-metabolic-diseases-and-the-modulatory-potential-by-medicinal-plant-and-food-ingredients
#11
REVIEW
Hoda M Eid, Michelle L Wright, N V Anil Kumar, Abdel Qawasmeh, Sherif T S Hassan, Andrei Mocan, Seyed M Nabavi, Luca Rastrelli, Atanas G Atanasov, Pierre S Haddad
Metabolic syndrome is a cluster of three or more metabolic disorders including insulin resistance, obesity, and hyperlipidemia. Obesity has become the epidemic of the twenty-first century with more than 1.6 billion overweight adults. Due to the strong connection between obesity and type 2 diabetes, obesity has received wide attention with subsequent coining of the term "diabesity." Recent studies have identified unique contributions of the immensely diverse gut microbiota in the pathogenesis of obesity and diabetes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712893/the-glucagon-like-peptide-1-analogue-liraglutide-promotes-autophagy-through-the-modulation-of-5-amp-activated-protein-kinase-in-ins-1-%C3%AE-cells-under-high-glucose-conditions
#12
Xinyu Miao, Zhaoyan Gu, Yu Liu, Mengmeng Jin, Yanhui Lu, Yanping Gong, Lin Li, Chunlin Li
Glucagon-like peptide-1 (GLP-1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic β-cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic β-cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP-1-induced protection of pancreatic β-cells exposed to high glucose...
July 13, 2017: Peptides
https://www.readbyqxmd.com/read/28711731/insulin-chains-as-efficient-fusion-tags-for-prokaryotic-expression-of-short-peptides
#13
Ligang Deng, Xiaoying Xue, Cangjie Shen, Xiaohan Song, Chunyang Wang, Nan Wang
Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting...
July 13, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28711685/misunderstandings-and-controversies-about-the-insulin-secreting-properties-of-antidiabetic-sulfonylureas
#14
REVIEW
Jean-Claude Henquin
After 60 years of use in the treatment of type 2 diabetes, hypoglycemic sulfonylureas remain a recommended option in current therapeutic charts. Their binding to sulfonylurea receptor-1, the regulatory subunit of ATP-sensitive potassium channels in the plasma membrane of pancreatic β-cells, leads to closure of the channels, membrane depolarization and influx of Ca(2+) through voltage-gated calcium channels. The resulting increase in cytosolic Ca(2+) triggers exocytosis of insulin granules. Sulfonylureas and glucose thus produce the same triggering signal but, unlike sulfonylureas, glucose does so via acceleration of β-cell metabolism...
July 12, 2017: Biochimie
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#15
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28710307/is-it-safe-to-acutely-discontinue-insulin-therapy-in-patients-with-chronic-hyperglycaemia-starting-glp-1r-agonists
#16
Julie Omolola Okiro, Catherine Mc Hugh, Abuelmagd Abdalla
We report two patients with chronic hyperglycaemia secondary to type 2 diabetes who developed severe vomiting on d. The first patient was diagnosed with a mixed picture of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) and the second, with DKA. They were on insulin therapy which was discontinued on commencing d because of inefficacy and weight gain. The HHS patient developed dehydration secondary to vomiting and had lactic acidosis but no other precipitant could be found in either case...
July 14, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28710249/amyloid-precursor-protein-in-pancreatic-islets
#17
Joshua Kulas, Kendra Puig, Colin K Combs
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque forming peptide in Alzheimer's disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well characterized consequence of type 1 and type 2 diabetes. In this study we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes...
July 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#18
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#19
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28707223/inhibition-of-exendin-4-induced-steatosis-by-protein-kinase-a-in-cultured-hepg2-human-hepatoma-cells
#20
Alice Y Chen-Liaw, Gabrielle Hammel, George Gomez
Nonalcoholic fatty liver is characterized by the abnormal accumulation of triglycerides within hepatocytes, resulting in a steatotic liver. Glucagon-like peptide 1 and its analog exendin-4 can ameliorate certain aspects of this syndrome by inducing weight loss and reducing hepatic triglyceride accumulation, but it is unclear whether these effects result from the effects of glucagon-like peptide 1 on the pancreas, or from direct action on the liver. This study investigated the direct action and putative cellular mechanism of exendin-4 on steatotic hepatocytes in culture...
July 13, 2017: In Vitro Cellular & Developmental Biology. Animal
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