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Delayed implantation insulin

Ulrich Rohde, Cecilie A Federspiel, Peter Vilmann, Ebbe Langholz, Steffen U Friis, Martin Krakauer, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. MATERIAL AND METHODS: Ten normal glucose tolerant (NGT) obese subjects and nine age, body weight and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and one (1w) and 26 weeks (26w) after implantation...
October 3, 2016: Diabetes, Obesity & Metabolism
Sharon E Mitchell, Camille Delville, Penelope Konstantopedos, Davina Derous, Cara L Green, Yingchun Wang, Jing-Dong J Han, Daniel E L Promislow, Alex Douglas, Luonan Chen, David Lusseau, John R Speakman
Calorie restriction (CR) delays the onset of age-related disease and extends lifespan in a number of species. When faced with reduced energy supply animals need to lower energy demands, which may be achieved in part by reducing physical activity (PA). We monitored changes in PA using implanted transmitters in male C57BL/6 mice in response to graded levels of CR (10 to 40%) or matched levels of graded protein restriction (PR) for 3 months. Mice were fed at lights out and ad libitum controls were limited to dark-phase feeding (12AL) or 24hr/day...
April 12, 2016: Oncotarget
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
Robert T Dauchy, Aaron E Hoffman, Melissa A Wren-Dail, John P Hanifin, Benjamin Warfield, George C Brainard, Shulin Xiang, Lin Yuan, Steven M Hill, Victoria P Belancio, Erin M Dauchy, Kara Smith, David E Blask
Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts...
December 2015: Comparative Medicine
Andrew R Pepper, Rena Pawlick, Boris Gala-Lopez, Amanda MacGillivary, Delfina M Mazzuca, David J G White, Philip M Toleikis, A M James Shapiro
BACKGROUND: Islet transplantation is a successful β-cell replacement therapy for selected patients with type 1 diabetes mellitus. Although high rates of early insulin independence are achieved routinely, long-term function wanes over time. Intraportal transplantation is associated with procedural risks, requires multiple donors, and does not afford routine biopsy. Stem cell technologies may require potential for retrievability, and graft removal by hepatectomy is impractical. There is a clear clinical need for an alternative, optimized transplantation site...
November 2015: Transplantation
Saurabh Singh, Sanjay Pandey, Anant Narayan Bhatt, Richa Chaudhary, Vikas Bhuria, Namita Kalra, Ravi Soni, Bal Gangadhar Roy, Daman Saluja, Bilikere S Dwarakanath
BACKGROUND: Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis...
2015: PloS One
Ming Ming, James Sinnett-Smith, Jia Wang, Heloisa P Soares, Steven H Young, Guido Eibl, Enrique Rozengurt
Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC) cells (PANC-1, MiaPaCa-2) with the isoquinoline alkaloid berberine (0.3-6 µM) inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70%) the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice...
2014: PloS One
Gili Bisker, Nicole M Iverson, Jiyoung Ahn, Michael S Strano
While implantable sensors such as the continuous glucose monitoring system have been widely studied, both experimentally and mathematically, relatively little attention has been applied to the potential of insulin sensors. Such sensors can provide feedback control for insulin infusion systems and pumps and provide platforms for the monitoring of other biomarkers in vivo. In this work, the first pharmacokinetic model of an affinity sensor is developed for insulin operating subcutaneously in the limit of where mass transfer across biological membranes reaches a steady state...
January 7, 2015: Advanced Healthcare Materials
Alice A Tomei, Vita Manzoli, Christopher A Fraker, Jaime Giraldo, Diana Velluto, Mejdi Najjar, Antonello Pileggi, R Damaris Molano, Camillo Ricordi, Cherie L Stabler, Jeffrey A Hubbell
Encapsulation of islets of Langerhans may represent a way to transplant islets in the absence of immunosuppression. Traditional methods for encapsulation lead to diffusional limitations imposed by the size of the capsules (600-1,000 μm in diameter), which results in core hypoxia and delayed insulin secretion in response to glucose. Moreover, the large volume of encapsulated cells does not allow implantation in sites that might be more favorable to islet cell engraftment. To address these issues, we have developed an encapsulation method that allows conformal coating of islets through microfluidics and minimizes capsule size and graft volume...
July 22, 2014: Proceedings of the National Academy of Sciences of the United States of America
Young Min Ju, Anthony Atala, James J Yoo, Sang Jin Lee
Standard reconstructive procedures for restoring normal function after skeletal muscle defects involve the use of existing host tissues such as muscular flaps. In many instances, this approach is not feasible and delays the rehabilitation process and restoration of tissue function. Currently, cell-based tissue engineering strategies have been used for reconstruction; however, donor tissue biopsy and ex vivo cell manipulation are required prior to implantation. The present study aimed to overcome these limitations by demonstrating mobilization of muscle cells into a target-specific site for in situ muscle regeneration...
October 2014: Acta Biomaterialia
Georgios D Agrogiannis, Stavros Sifakis, Efstratios S Patsouris, Anastasia E Konstantinidou
The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis...
August 2014: Molecular Medicine Reports
Lin Wang, Lan Cao, Janet Shansky, Zheng Wang, David Mooney, Herman Vandenburgh
Repair of injured skeletal muscle by cell therapies has been limited by poor survival of injected cells. Use of a carrier scaffold delivering cells locally, may enhance in vivo cell survival, and promote skeletal muscle regeneration. Biomaterial scaffolds are often implanted into muscle tissue through invasive surgeries, which can result in trauma that delays healing. Minimally invasive approaches to scaffold implantation are thought to minimize these adverse effects. This hypothesis was addressed in the context of a severe mouse skeletal muscle injury model...
August 2014: Molecular Therapy: the Journal of the American Society of Gene Therapy
E Leifke, T R Strack
Subcutaneous (SC) insulin therapy has been a mainstay of pharmacological diabetes management from the moment insulin was successfully developed as treatment. Insulin formulations have become more refined and less allergenic over time, and ancillary technologies such as injection devices and glucose measurement tools have evolved to the extent of permitting closed-loop therapy. However, investigations have continued exploring alternative routes of administration with the ultimate goal of implantable islet replacements, whether cell- or "silicon"-based...
February 2014: Drugs of Today
Wenjuan Zhou, Zhonghao Liu, Jie Yao, Fei Chi, Kai Dong, Xilong Yue, Teng Teng, Xiaohui Rausch
PURPOSE: The aim of this project is to investigate the impact of diabetes mellitus and different glycemic control times on early osseointegration of dental implants by expression and significance of serum bone Gla protein (BGP) and alkaline phosphatase (ALP) levels in Zucker diabetic fatty (ZDF) rats after implantation. MATERIALS AND METHODS: The animals were divided into three groups, each group with 11 rats and each rat with two dental implants (33 rats and 66 implants in total): group A, diabetic rats with dental implants (controls); group B, diabetic rats treated with insulin and implants placed simultaneously; and group C, diabetic rats treated with insulin until serum glucose at a constant level and then implants be placed...
August 2015: Clinical Implant Dentistry and related Research
Britta S Nelson, Rachel C Springer, Jill M Daniel
RATIONALE: Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1). OBJECTIVE: The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1...
March 2014: Psychopharmacology
Fei Wu, Lili Guo, Aniela Jakubowski, Lihe Su, Wan-Chun Li, Susan Bonner-Weir, Linda C Burkly
AIM/HYPOTHESIS: The adult mammalian pancreas has limited ability to regenerate in order to restore adequate insulin production from multipotent progenitors, the identity and function of which remain poorly understood. Here we test whether the TNF family member TWEAK (TNF-like weak inducer of apoptosis) promotes β-cell neogenesis from proliferating pancreatic ductal epithelium in adult mice. METHODS: C57Bl/6J mice were treated with Fc-TWEAK and pancreas harvested at different time points for analysis by histology and immunohistochemistry...
2013: PloS One
Nina Sauer, Thomas Rösch, Jennifer Pezold, Franziska Reining, Mario Anders, Stefan Groth, Guido Schachschal, Oliver Mann, Jens Aberle
BACKGROUND: The endoluminal mechanical device SatiSphere is a new endoscopically implantable device designed to delay transit time of nutrients through the duodenum. It consists of a 1-mm nitinol wire with pigtail ends and several mesh spheres mounted along its course, released in the duodenum and gastric antrum to conform to the duodenal C loop configuration and thereby self-anchor. METHODS: The objective is to test the safety, efficacy, and effect on body weight in a 2:1 randomized study, as well as incretin secretion in a subgroup...
November 2013: Obesity Surgery
Cinzia Di Pietro, Ettore Cicinelli, Maria R Guglielmino, Marco Ragusa, Marco Farina, Marco A Palumbo, Antonio Cianci
PROBLEM: Chronic endometritis (CE) is a poorly investigated and probably underestimated pathology, which may cause abnormal uterine bleeding (AUB), pain, and reproductive failures. Due to undefined symptoms and the normal presence of leukocytes in the endometrial mucosa, diagnosis may be missed. Fluid hysteroscopy is a reliable technique for diagnosing this pathology. Few data exist on the biochemical and paracrine alterations that occur in the endometrium of women diagnosed with CE. The aim of the study was to find molecular modification in endometrium related to CE...
May 2013: American Journal of Reproductive Immunology: AJRI
John D Koerner, Praveen Yalamanchili, William Munoz, Linda Uko, Saad B Chaudhary, Sheldon S Lin, Michael J Vives
BACKGROUND CONTEXT: The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a time-released insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry...
January 2013: Spine Journal: Official Journal of the North American Spine Society
Robert B Vernon, Anton Preisinger, Michel D Gooden, Leonard A D'Amico, Betty B Yue, Paul L Bollyky, Christian S Kuhr, Thomas R Hefty, Gerald T Nepom, John A Gebe
We have developed a bioengineered implant (BI) to evaluate strategies to promote graft survival and function in models of islet transplantation in mice. The BI, sized for implantation within a fold of intestinal mesentery, consists of a disk-shaped, polyvinyl alcohol sponge infused with a type I collagen hydrogel that contains dispersed donor islets. To promote islet vascularization, the BI incorporates a spherical alginate hydrogel for sustained release of vascular endothelial growth factor (VEGF). BIs that contained 450-500 islets from syngeneic (C57Bl/6) donors and 20 ng of VEGF reversed streptozotocin (STZ)-induced diabetes in 100% of mice (8/8), whereas BIs that contained an equivalent number of islets, but which lacked VEGF, reversed STZ-induced diabetes in only 62...
2012: Cell Transplantation
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