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Insulin receptor implantation

Mingwei Huang, Liucheng Wu, Yuzhou Qin, Zhao Li, Shanshan Luo, Haiquan Qin, Yang Yang, Jiansi Chen
Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays...
2016: American Journal of Translational Research
Hsu-Tung Lee, Hao-Teng Chang, Sophie Lee, Chen-Huan Lin, Jia-Rong Fan, Shinn-Zong Lin, Chung Y Hsu, Chia-Hung Hsieh, Woei-Cherng Shyu
To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)-expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB)...
2016: Scientific Reports
Farah Lizotte, Benoit Denhez, Andréanne Guay, Nicolas Gévry, Anne Marie Côté, Pedro Geraldes
Poor glycemic control profoundly impacts protein expression and cell signaling action that contributes to glycemic memory and irreversible progression of diabetic nephropathy (DN). We have demonstrated that SHP-1 is elevated in podocytes of diabetic mice causing insulin unresponsiveness and DN. Thus, sustained SHP-1 expression caused by hyperglycemia despite systemic glucose normalization could contribute to the glycemic memory effect in DN. Microalbuminuria, GFR, mesangial cell expansion, collagen IV and TGF-β expression were significantly increased in diabetic Ins2(+/C96Y) mice compared to non-diabetic Ins2(+/+) mice and remained elevated despite glucose normalization with insulin implants...
September 1, 2016: Diabetes
Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen
BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system...
August 30, 2016: Obesity Surgery
N Smolinska, K Dobrzyn, M Kiezun, K Szeszko, A Maleszka, T Kaminski
Adiponectin and its receptors are expressed in the human and porcine uterus and this endocrine system has important role in the regulation of reproductive processes. The expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (HSD3B1) were observed in the human and porcine uterus during the oestrous cycle and pregnancy. The de novo synthesis of steroids in the uterus might be a crucial factor for effective implantation and maintenance of pregnancy. We hypothesized that adiponectin modulates the expression of key enzymes in the synthesis of the steroids: StAR, P450 side chain cleavage enzyme (CYP11A1) and HSD3B1, as well as progesterone (P4) and androstenedione (A4) secretion by the porcine uterus...
June 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
C S Filgueira, E Nicolov, R L Hood, A Ballerini, J Garcia-Huidobro, J Z Lin, D Fraga, P Webb, O M Sabek, A O Gaber, K J Phillips, A Grattoni
BACKGROUND/OBJECTIVES: Our objective was to assess the sustained, low-dose and constant administration of the thyroid receptor beta (TRβ)-selective agonist GC-1 (sobetirome) from a novel nanochannel membrane device (NMD) for drug delivery. As it known to speed up metabolism, accomplish weight loss, improve cholesterol levels, and possess anti-diabetic effects, GC-1 was steadily administered by our NMD, consisting of an implantable nanochannel membrane, as an alternative to conventional daily administration, which is subject to compliance issues in clinical settings...
July 27, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
William B Hillegass
Insulin treatment for diabetes is a simple but important risk marker for doubled adjusted death and myocardial infarction rates and tripled stent thrombosis risk after coronary stenting. Insulin treatment does not predict meaningfully increased major bleeding or additional revascularization procedures after drug eluting coronary stent implantation. Third generation P2 Y12 receptor antagonists substantially lower risk of events in diabetics after stenting with insulin treated diabetics having twice the magnitude of benefit of diabetics not needing insulin...
January 1, 2016: Catheterization and Cardiovascular Interventions
Sarah A Marshall, Sevvandi N Senadheera, Laura J Parry, Jane E Girling
The hormone relaxin is a 6-kDa peptide with high structural similarity to insulin. It is primarily produced by the corpus luteum during pregnancy but is also synthesized by other reproductive organs such as the uterus, decidua, and placenta. Relaxin binds to its receptor RXFP1, which has been localized to a wide variety of reproductive and nonreproductive tissues. The peptide's many uterotropic effects include stimulating uterine growth and vascularization, remodeling extracellular matrix components, and regulating vascular endothelial growth factor in preparation for implantation...
June 29, 2016: Reproductive Sciences
Sean Carrig, Enoch Bijjiga, Mitchell J Wopat, Ashley Martino
AAV (adeno-associated virus) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions i.e. Alpha-1-antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhances transduction of liver and skeletal muscle using these vectors is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored...
June 29, 2016: Human Gene Therapy
Takashi Murakami, Arun S Singh, Tasuku Kiyuna, Sarah M Dry, Yunfeng Li, Aaron W James, Kentaro Igarashi, Kei Kawaguchi, Jonathan C DeLong, Yong Zhang, Yukihiko Hiroshima, Tara Russell, Mark A Eckardt, Jane Yanagawa, Noah Federman, Ryusei Matsuyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Fritz C Eilber, Robert M Hoffman
Ewing's sarcoma is a rare and aggressive malignancy. In the present study, tumor from a patient with a Ewing's sarcoma with cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss and FUS-ERG fusion was implanted in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present study was to determine efficacy of cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors on the Ewing's sarcoma PDOX. The PDOX models were randomized into the following groups when tumor volume reached 50 mm3: G1, untreated control; G2, doxorubicin (DOX) (intraperitoneal (i...
June 7, 2016: Oncotarget
Matthew W McDonald, Michael R Murray, Kenneth N Grise, T Dylan Olver, Adwitia Dey, J Kevin Shoemaker, Earl G Noble, C W James Melling
An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague-Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8)...
June 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Omonseigho O Talton, Kathleen A Pennington, Kelly E Pollock, Keenan Bates, Lixin Ma, Mark R Ellersieck, Laura C Schulz
Maternal obesity and gestational diabetes are prevalent worldwide. Offspring of mothers with these conditions weigh more and are predisposed to metabolic syndrome. A hallmark of both conditions is maternal hyperleptinemia, but the role of elevated leptin levels during pregnancy on developmental programming is largely unknown. We previously found that offspring of hyperleptinemic mothers weighed less and had increased activity. The goal of this study was to determine whether maternal leptin affects offspring insulin sensitivity by investigating offspring glucose metabolism and lipid accumulation...
July 2016: Endocrinology
A Guzmán, E Gonzalez-Padilla, P Garcés-Yepez, J V Rosete-Fernández, R C Calderón-Robles, W D Whittier, D H Keisler, C G Gutierrez
Energy reserve, estimated as body condition score (BCS), is the major determinant of the re-initiation of ovarian activity in postpartum cows. Leptin, IGF-I and insulin are positively related to BCS and are putative mediators between BCS and reproductive function. However, when BCS and body composition dissociates, concentrations of these metabolic hormones are altered. We hypothesized that increasing lean muscle tissue, but not fat tissue, would diminish the reproductive response to oestrus induction treatments...
October 2016: Animal: An International Journal of Animal Bioscience
Christopher G England, Anyanee Kamkaew, Hyung-Jun Im, Hector F Valdovinos, Haiyan Sun, Reinier Hernandez, Steve Y Cho, Edward J Dunphy, Dong Soo Lee, Todd E Barnhart, Weibo Cai
The role of insulin-like growth factor-1 receptor (IGF-1R) in cancer tumorigenesis was established decades ago, yet there are limited studies evaluating the imaging and therapeutic properties of anti-IGF-1R antibodies. Noninvasive imaging of IGF-1R may allow for optimized patient stratification and monitoring of therapeutic response in patients. Herein, this study reports the development of a Zirconium-89 ((89)Zr)-labeled anti-IGF-1R antibody ((89)Zr-Df-1A2G11) for PET imaging of pancreatic cancer. Successful chelation and radiolabeling of the antibody resulted in a highly stable construct that could be used for imaging IGF-1R expressing tumors in vivo...
June 6, 2016: Molecular Pharmaceutics
Xiao Li, Pengfei Lin, Fenglei Chen, Nan Wang, Fan Zhao, Aihua Wang, Yaping Jin
Decidualization is crucial for successful pregnancy in mice and humans. Although many essential molecular modulators have been identified during decidualization, the precise molecular mechanism of uterine decidualization remains largely unknown. Our previous research indicates that luman recruiting factor (LRF) is strongly expressed in decidual uteri of mice on days 6-8 of pregnancy. In this study, our aim is to determine the biological functions of LRF during decidualization in mice. We used the shLRF lentivirus to attenuate the expression of LRF, which significantly reduced the weight and size of implantation sites on days 7-8 of pregnancy...
August 2016: Cell and Tissue Research
Jill S Carmody, Rodrigo Muñoz, Huali Yin, Lee M Kaplan
Roux-en-Y gastric bypass (RYGB) causes profound weight loss and remission of diabetes by influencing metabolic physiology, yet the mechanisms behind these clinical improvements remain undefined. After RYGB, levels of glucagon-like peptide-1 (GLP-1), a hormone that enhances insulin secretion and promotes satiation, are substantially elevated. Because GLP-1 signals in both the periphery and the brain to influence energy balance and glucose regulation, we aimed to determine the relative requirements of these systems to weight loss and improved glucose tolerance following RYGB surgery in mice...
May 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
E S Ribeiro, A P A Monteiro, R S Bisinotto, F S Lima, L F Greco, A D Ealy, W W Thatcher, J E P Santos
The objectives were to compare development and transcriptome of preimplantation conceptuses 15 d after synchronized ovulation and artificial insemination (AI) according to the genetic background of the cow and estrous cyclicity at the initiation of the synchronization program. On d 39±3 postpartum, Holstein cows that were anovular (HA; n=10), Holstein cows that were estrous cyclic (HC; n=25), and Jersey/Holstein crossbred cows that were estrous cyclic (CC; n=25) were randomly selected in a grazing herd and subjected to the Ovsynch protocol...
June 2016: Journal of Dairy Science
Sarah A Stanley, Leah Kelly, Kaamashri N Latcha, Sarah F Schmidt, Xiaofei Yu, Alexander R Nectow, Jeremy Sauer, Jonathan P Dyke, Jonathan S Dordick, Jeffrey M Friedman
Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP-TRPV1)...
March 31, 2016: Nature
Srilatha Swami, Aruna V Krishnan, Jasmaine Williams, Abhishek Aggarwal, Megan A Albertelli, Ronald L Horst, Brian J Feldman, David Feldman
Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, and all contribute to increased synthesis of mammary estrogens, the drivers of estrogen receptor-positive (ER+) BCa growth. As both dietary vitamin D and calcitriol treatments inhibit breast estrogen synthesis and signaling, we hypothesized that vitamin D would be especially beneficial in mitigating the adverse effects of obesity on ER+BCa. To assess whether obesity exerted adverse effects on BCa growth and whether vitamin D compounds could reduce these unfavorable effects, we employed a diet-induced obesity (DIO) model in ovariectomized C57BL/6 mice...
April 2016: Endocrine-related Cancer
Clifford J Bailey, Abd A Tahrani, Anthony H Barnett
The multivariable and progressive natural history of type 2 diabetes limits the effectiveness of available glucose-lowering drugs. Constraints imposed by comorbidities (notably cardiovascular disease and renal impairment) and the need to avoid hypoglycaemia, weight gain, and drug interactions further complicate the treatment process. These challenges have prompted the development of new formulations and delivery methods for existing drugs alongside research into novel pharmacological entities. Advances in incretin-based therapies include a miniature implantable osmotic pump to give continuous delivery of a glucagon-like peptide-1 receptor agonist for 6-12 months and once-weekly tablets of dipeptidyl peptidase-4 inhibitors...
April 2016: Lancet Diabetes & Endocrinology
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