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https://www.readbyqxmd.com/read/28530382/diabetes-update-new-pharmacotherapy-for-type-2-diabetes
#1
Beth Choby
Multiple new drugs for managing type 2 diabetes have entered the market in the past 5 years. Guidelines from the American Diabetes Association recommend metformin for initial therapy, followed by a second drug if A1c goals are not met or initially for patients with A1c levels greater than 9%. Conversely, the American Association of Clinical Endocrinologists recommends initial management with two drugs if the A1c level is greater than 7.5%. The risk of lactic acidosis associated with metformin has been shown to be less than previously thought, with newer guidelines permitting use with an estimated glomerular filtration rate of 45 to 60 mL/min/1...
May 2017: FP Essentials
https://www.readbyqxmd.com/read/28529732/microarray-analysis-of-differentially-expressed-genes-and-their-functions-in-omental-visceral-adipose-tissues-of-pregnant-women-with-vs-without-gestational-diabetes-mellitus
#2
Yuan Qian, Hao Sun, Hongli Xiao, Meirun Ma, Xue Xiao, Qinzai Qu
Increasing evidence has shown that insulin resistance in omental visceral adipose tissue (OVAT) is a characteristic of gestational diabetes mellitus (GDM). The present study aimed to identify differentially expressed genes (DEGs) and their associated functions and pathways involved in the pathogenesis of GDM by comparing the expression profiles of OVATs obtained from pregnant Chinese women with and without GDM during caesarian section. A total of 935 DEGs were identified, including 450 downregulated and 485 upregulated genes...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28529580/microrna-592-targets-igf-1r-to-suppress-cellular-proliferation-migration-and-invasion-in-hepatocellular-carcinoma
#3
Wenyao Wang, Hongfei Zhang, Mao Tang, Longlong Liu, Zhengfang Zhou, Shaojun Zhang, Lichao Wang
MicroRNAs (miRs) can function as tumor suppressors or oncogenes in different types of human malignancy, and may provide an effective therapy for cancer. The expression and functions of miR-592 have previously been studied in relation to cancer. However, the expression and potential functions of miR-592 in hepatocellular carcinoma (HCC) are still unknown. Using quantitative polymerase chain reaction, MTT assays, cellular migration and invasion assays, bioinformatics software, western blot analysis and dual-luciferase report assays, the present study explored the expression and roles of miR-592 in HCC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529539/jiangtang-decoction-ameliorate-diabetic-nephropathy-through-the-regulation-of-pi3k-akt-mediated-nf-%C3%AE%C2%BAb-pathways-in-kk-ay-mice
#4
Jin-Ni Hong, Wei-Wei Li, Lin-Lin Wang, Hao Guo, Yong Jiang, Yun-Jia Gao, Peng-Fei Tu, Xue-Mei Wang
BACKGROUND: Jiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28529141/z-505-hydrochloride-an-orally-active-ghrelin-agonist-attenuates-the-progression-of-cancer-cachexia-via-anabolic-hormones-in-colon-26-tumor-bearing-mice
#5
Makoto Yoshimura, Yoshihiro Shiomi, Yuta Ohira, Mineo Takei, Takao Tanaka
Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505...
May 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28528971/regulatory-effects-of-4-methoxychalcone-on-adipocyte-differentiation-through-ppar%C3%AE-activation-and-reverse-effect-on-tnf-%C3%AE-in-3t3-l1-cells
#6
Younho Han, Sung Ho Lee, Ik-Soo Lee, Kwang Youl Lee
Chalcones, the biosynthetic precursors of flavonoids and isoflavonoids abundant in edible plants, possess a number of pharmacological properties, and there is growing evidence that chalcone derivatives inhibit TNF-α mediated insulin resistance. The aim of the present study was to define the effects of 4-methoxychalcone (4-MC) on adipocyte differentiation and to determine the underlying molecular mechanism. We investigated the effects of 4-MC on adipocyte differentiation and lipid accumulation, and expression of adipogenic genes in 3T3-L1 cells...
May 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28528692/insulin-like-growth-factor-igf-axis-in-cancerogenesis
#7
REVIEW
Aldona Kasprzak, Wojciech Kwasniewski, Agnieszka Adamek, Anna Gozdzicka-Jozefiak
Determination of the role of insulin-like growth factor (IGF) family components in carcinogenesis of several human tumors is based on numerous epidemiological and pre-clinical studies, experiments in vivo and in vitro and on attempts at application of drugs affecting the IGF axis. Investigative hypotheses in original studies were based on biological functions manifested by the entire family of IGF (ligands, receptors, linking proteins, adaptor molecules). In the context of carcinogenesis the most important functions of IGF family involve intensification of proliferation and inhibition of cell apoptosis and effect on cell transformation through synthesis of several regulatory proteins...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28528691/the-igf-axis-in-hpv-associated-cancers
#8
REVIEW
Adam Pickard, Julia Durzynska, Dennis J McCance, Elisabeth R Barton
Human papillomaviruses (HPV) infect and replicate in stratified epithelium at cutaneous and mucosal surfaces. The proliferation and maintenance of keratinocytes, the cells which make up this epithelium, are controlled by a number of growth factor receptors such as the keratinocyte growth factor receptor (KGFR, also called fibroblast growth factor receptor 2b (FGFR2b)), the epithelial growth factor receptor (EGFR) and the insulin-like growth factor receptors 1 and 2 (IGF1R and IGF2R). In this review, we will delineate the mutation, gene transcription, translation and processing of the IGF axis within HPV associated cancers...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28528684/clinical-studies-in-humans-targeting-the-various-components-of-the-igf-system-show-lack-of-efficacy-in-the-treatment-of-cancer
#9
REVIEW
Anastassios Philippou, Panagiotis F Christopoulos, Dr Michael Koutsilieris
The insulin-like growth factors (IGFs) system regulates cell growth, differentiation and energy metabolism and plays crucial role in the regulation of key aspects of tumor biology, such as cancer cell growth, survival, transformation and invasion. The current focus for cancer therapeutic approaches have shifted from the conventional treatments towards the targeted therapies and the IGF system has gained a great interest as anti-cancer therapy. The proliferative, anti-apoptotic and transformation effects of IGFs are mainly triggered by the ligation of the type I IGF receptor (IGF-IR)...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28528294/isoliquiritigenin-reduces-oxidative-damage-and-alleviates-mitochondrial-impairment-by-sirt1-activation-in-experimental-diabetic-neuropathy
#10
Veera Ganesh Yerra, Anil Kumar Kalvala, Ashutosh Kumar
Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells...
May 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28527797/mir-26b-promoter-analysis-reveals-regulatory-mechanisms-by-lipid-related-transcription-factors-in-goat-mammary-epithelial-cells
#11
Hui Wang, Jun Luo, Qiuya He, Dawei Yao, Jiao Wu, Juan J Loor
MicroRNA (miRNA) regulate protein abundance and control diverse aspects of cellular processes and biological functions associated with lipid metabolism. MiR-26b and its host gene CTDSP1 regulate triacylglycerol synthesis by synergistically suppressing the insulin-induced gene 1 (INSIG1); however, the direct regulators of miR-26b expression remain unknown. In the present study, we characterized the activity of a novel putative promoter region in miR-26b. Results revealed that promoter activity and miR-26b expression are dynamically regulated by different transcription factors including peroxisome proliferator-activated receptor gamma (PPARG), sterol regulatory element binding transcription factor 1 (SREBF1), and liver X receptor α (LXRα)...
May 17, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28527578/tr2-and-tr4-orphan-nuclear-receptors-an-overview
#12
Shin-Jen Lin, Dong-Rong Yang, Guosheng Yang, Chang-Yi Lin, Hong-Chiang Chang, Gonghui Li, Chawnshang Chang
Testicular nuclear receptors 2 and 4 (TR2, TR4), also known as NR2C1 and NR2C2, belong to the nuclear receptor superfamily and were first cloned in 1989 and 1994, respectively. Although classified as orphan receptors, several natural molecules, their metabolites, and synthetic compounds including polyunsaturated fatty acids (PUFAs), PUFA metabolites 13-hydroxyoctadecadienoic acid, 15-hydroxyeicosatetraenoic acid, and the antidiabetic drug thiazolidinediones can transactivate TR4. Importantly, many of these ligands/activators can also transactivate peroxisome proliferator-activated receptor gamma (PPARγ), also known as NR1C3 nuclear receptor...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28527131/impact-of-muscarinic-m3-receptor-antagonism-on-the-risk-of-type-2-diabetes-in-antidepressant-treated-patients-a-case-controlled-study
#13
Yen-Hao Tran, Catharina C M Schuiling-Veninga, Jorieke E H Bergman, Henk Groen, Bob Wilffert
BACKGROUND: M3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion. OBJECTIVE: Our objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M3 muscarinic receptor antagonism (AD_antaM3 and AD_nonantaM3, respectively). METHODS: We designed a case-control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline...
May 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#14
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526811/proteomic-analysis-of-cerebrospinal-fluid-from-children-with-central-nervous-system-tumors-identifies-candidate-proteins-relating-to-tumor-metastatic-spread
#15
Filippo Spreafico, Italia Bongarzone, Sara Pizzamiglio, Ruben Magni, Elena Taverna, Maida De Bortoli, Chiara M Ciniselli, Elena Barzanò, Veronica Biassoni, Alessandra Luchini, Lance A Liotta, Weidong Zhou, Michele Signore, Paolo Verderio, Maura Massimino
Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS)...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526658/nonclinical-pharmacology-and-toxicology-of-the-first-biosimilar-insulin-glargine-drug-product-basaglar-%C3%A2-abasaglar-%C3%A2-approved-in-the-european-union
#16
Richard A Byrd, Rebecca A Owens, Jamie L Blackbourne, David E Coutant, Mark W Farmen, M Dodson Michael, Julie S Moyers, A Eric Schultze, Michael K Sievert, Niraj K Tripathi, John L Vahle
Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity...
May 16, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28526479/foxo-mediates-the-timing-of-pupation-through-regulating-ecdysteroid-biosynthesis-in-the-red-flour-beetle-tribolium-castaneum
#17
Xianyu Lin, Na Yu, Guy Smagghe
The steroid hormone 20-hydroxyecdysone (20E), the major developmental hormone in insects, controls all the developmental transitions including ecdysis and metamorphosis. In our study with last larval stages of the red flour beetle, Tribolium castaneum, dsRNA-mediated gene silencing of Forkhead box protein O (FoxO) resulted in reduced food intake and larval mass and this agreed with a reduction in the expression of insulin signaling-related genes (insulin-like peptides 2, 3, 4, and chico). Interestingly, we also observed a significant delay in the moment of the pupation and these FoxO-silenced larvae then died at the middle pupal stage...
May 16, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#18
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28526033/effects-of-exenatide-on-cardiac-function-perfusion-and-energetics-in-type-2-diabetic-patients-with-cardiomyopathy-a-randomized-controlled-trial-against-insulin-glargine
#19
Weena J Y Chen, Michaela Diamant, Karin de Boer, Hendrik J Harms, Lourens F H J Robbers, Albert C van Rossum, Mark H H Kramer, Adriaan A Lammertsma, Paul Knaapen
BACKGROUND: Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored...
May 19, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#20
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
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