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Insulin receptor implantation

Ann Marie O'Neill, Christine M Burrington, Erin A Gillaspie, Darin T Lynch, Melissa J Horsman, Michael W Greene
Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth...
October 20, 2016: Nutrition Research
Daniel Espes, Ramkumar Selvaraju, Irina Velikyan, Martin Krajcovic, Per-Ola Carlsson, Olof Eriksson
BACKGROUND: There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor β-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular β-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys(40)-Exendin-4...
August 2016: Transplantation Direct
Ulrich Rohde
Bariatric surgery (e.g. Roux-en-Y gastric bypass (RYGB)) has proven the most effective way of achieving sustainable weight losses and remission of type 2 diabetes (T2D). Studies indicate that the effectiveness of RYGB is mediated by an altered gastrointestinal tract anatomy, which in particular favours release of the gut incretin hormone glucagon-like peptide-1 (GLP-1). The EndoBarrier gastrointestinal liner or duodenal-jejunal bypass sleeve (DJBS) is an endoscopic deployable minimally invasive and fully reversible technique designed to mimic the bypass component of the RYGB...
November 2016: Danish Medical Journal
L Balazova, K Krskova, M Suski, V Sisovsky, N Hlavacova, R Olszanecki, D Jezova, S Zorad
Increasing evidence indicates a role of oxytocin in controlling energy metabolism. The aim of his study was to investigate oxytocin effects on obese phenotype in leptin-resistant Zucker fatty rats, focusing on glucose and lipid metabolism. Zucker fatty rats and their lean controls were treated with oxytocin (3.6 μg/100g body weight/day) by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hours intraperitoneal glucose tolerance test was performed in fasting rats. Oxytocin decreased food intake in both phenotypes while body weight gain reduced only in obese animals...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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-β (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...
November 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 T Martino
Adeno-associated virus (AAV) 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, that is, α1-antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance 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...
November 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
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