DOCSLIB.ORG

Gut and Adipocyte Peptides

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gut and Adipocyte Peptides Reviews/Commentaries/ADA Statements PERSPECTIVES ON THE NEWS Gut and Adipocyte Peptides ZACHARY T. BLOOMGARDEN, MD sented information pertaining to effects of GLP-1 on insulin action, noting that a ma- jor confounding factor is the increase in his is the third in a series of articles els are increased. The perfused pancreas portal insulin levels and the decrease in Ϫ Ϫ on presentations at the American isolated from GLP-1R / animals shows glycemia with GLP-1, both indirectly im- T Diabetes Association Annual Meet- normal insulin response to glucose, proving the glucose-lowering effect of insu- ing, San Diego, California, 10–14 June although without response to GLP-1. GLP- lin. GLP-1 concentrations are somewhat Ϫ Ϫ 2005. 1R / ␤-cells appear to have increased sen- lower in persons with diabetes and, to a sitivity to the incretin glucose-dependent lesser extent, with impaired glucose toler- Glucagon-like peptide-1 (and related insulinotropic polypeptide (GIP), perhaps ance, and GLP-1R activation is increased hormones) representing an adaptive upregulation of well beyond the physiologic range both Daniel Drucker (Toronto, Canada) re- GIP and/or of GIP response, and mice nei- with agonists and with administration of viewed evidence that the incretin effect, ther expressing the GLP-1 nor the GIP re- DPP-IV inhibitors. In vitro, GLP-1 increases the phenomenon of enteral glucose load- ceptor show glucose intolerance with adipocyte 2-deoxy-glucose uptake, rat so- ing increasing the insulin secretory re- decreased insulin response to glucose, and leus muscle glycogen synthesis, and hep- sponse to an increase in blood glucose, is fail to show a glucose-lowering response taocyte glycogen synthase A levels. In reduced in type 2 diabetes, and that the with administration of DPP-IV inhibitors, mouse models, the effect of insulin in in- incretin glucagon-like peptide (GLP)-1 suggesting that the mechanism of DPP-IV creasing glucose uptake is enhanced with- may ameliorate this defect. The major inhibition involves both peptides. GLP- out change in glucose effectiveness by Ϫ Ϫ limitation to use of GLP-1 in clinical treat- 1R / mice have increased ␤-cell suscepti- administration of GLP-1. In obese hyper- ment is its rapid clearance by the enzyme bility to apoptotic streptozotocin injury. In glycemic Zucker rats, administration of ex- Ϫ Ϫ dipeptidyl peptidase (DPP)-IV. GLP-1 the ob/ob (leptin-deficient) GLP-1R / enatide increases the glucose infusion rate stimulates insulin secretion, inhibits glu- mouse, insulin gene levels are upregulated required to maintain euglycemia, suggest- cagon secretion, and delays gastric emp- and there is islet hyperplasia to the same ing increased insulin action. In nondiabetic tying. Loss-of-function studies with a extent as seen in the ob/ob mouse with nor- humans, however, the glucose dis- mouse model not expressing the GLP-1 mal GLP-1R function. With partial pancre- appearance rate with peripheral infusion of Ϫ Ϫ receptor (GLP-1R / ), and with the atectomy, however, although exendin-(9- GLP-1 is equal to that with insulin infusion GLP-1R antagonist exendin-(9-39), show 39) does not block ␤-cell hyperplasia, the to produce similar insulin levels. A measure Ϫ Ϫ effects of GLP-1 on the hypothalamic- GLP-1R / mouse has reduced ␤-cell re- of “glucose effectiveness” appears to be in- pituitary-adrenal (HPA) axis, the repro- generation and is hyperglycemic. Taken to- creased in persons without diabetes admin- ductive system, the portal glucose gether, these studies suggest that trophic istered GLP-1, but Rizza showed another receptor, gastric motility, and a number of effects of GLP-1 on the ␤-cell occur physi- study of persons with type 2 diabetes, in Ϫ Ϫ other potential targets. GLP-1R / mice ologically. There are areas with high density which GLP-1 increased insulin and reduced have normal insulin sensitivity, arguing of GLP-1R binding sites in the hypothala- glucose levels modestly, without change in against an effect of the system on insulin mus, but their role is uncertain. The GLP- glucose effectiveness with insulin clamped. Ϫ Ϫ action, but have glucose intolerance, and 1R / mouse has normal body weight and In a 6-week study of persons with type 2 administration of exendin-(9-39) simi- minimal perturbation in food ingestion on a diabetes undergoing continuous GLP-1 in- larly is associated with glucose intoler- standard diet, although showing lesser de- fusion, the glucose infusion requirement ance in mice, in primates, and in humans. grees of obesity on a high-fat diet. Gastric was increased during a hyperinsulinemic- Ϫ Ϫ Drucker noted that there is controversy as emptying is not changed in the GLP-1R / euglycemic clamp, although with some- to whether the product of DPP-IV degra- mouse, which shows a response to chole- what lower glucose levels, potentially dation may act at a second GLP-1R, per- cystokinin although not to exendin. Studies explaining improved insulin sensitivity (1). haps having additional effects on in these mice also suggest that there is a Rizza showed an interesting study in per- metabolism, but that GLP-1 does not neural portal vein and/or liver glucose sen- Ϫ Ϫ sons with type 1 diabetes, with glucose in- lower glucose levels in GLP-1R / mice, sor, which may be in part activated by fusion rates during a euglycemic clamp arguing against such a receptor. In the GLP-1 to enhance the response to ingested modestly increased by GLP-1, again sug- model, pancreatic insulin mRNA levels food. gesting possible effect on insulin action. are reduced and somatostatin mRNA lev- Robert Rizza (Rochester, MN) pre- David D’Alessio (Cincinnati, OH) dis- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● cussed the effect of GLP-1 on body weight. Central administration of GLP-1 Zachary T. Bloomgarden, MD, is a practicing endocrinologist in New York, New York, and is affiliated with decreases, whereas that of exendin-(9-39) the Division of Endocrinology, Mount Sinai School of Medicine, New York, New York. Abbreviations: AGRP, agouti-related peptide; ARIC, Atherosclerosis Risk in Communities; BBB, blood- increases food intake (2). There is a taste- brain barrier; CART, cocaine-amphetamine–regulated transcript; CNTF, ciliary neurotrophic factor; DPP, aversive effect of central GLP-1, not seen dipeptidyl peptidase; FFA, free fatty acid; GIP, glucose-dependent insulinotropic polypeptide; GLP, gluca- with leptin in doses similarly decreasing gon-like peptide; GLP-1R, GLP-1 receptor; MCH, melanin-concentrating hormone; NPY, neuropeptide Y; food intake (3). Furthermore, central ad- NTS, nucleus of the solitary tract; POMC, proopiomelanocortin; PPAR, peroxisome proliferator–activated receptor; REE, resting energy expenditure; SOCS, suppressor of cytokine signaling; STAT, signal transducers ministration of GLP-1 induces neuronal and activators of transcription; TLR, toll-like receptor; TNF, tumor necrosis factor. growth in central emetic areas. Thus, © 2006 by the American Diabetes Association. GLP-1 may suppress food intake by acting 450 DIABETES CARE, VOLUME 29, NUMBER 2, FEBRUARY 2006 Bloomgarden as a satiety factor, as a regulator of energy ministration of central GLP-1R agonists, sion, glucose levels are reduced, with balance like leptin or insulin, or intrigu- so that ongoing suppression of appetite suggestion of improvement in insulin ingly, as a mediator of a “visceral illness” and weight loss can be expected to occur, sensitivity. As GLP-1 is rapidly inacti- response. Examining the brain GLP-1 sys- although the mechanisms of these vated by DPP-IV, which cleaves alanine or tem, the nucleus of the solitary tract chronic effects may differ from those of proline at the second amino acid of the (NTS) receives signals from gut visceral GLP-1 administered acutely. NH2-terminal of the peptide, the two afferents and contains a small number of Peripheral infusions of supraphysi- strategies that have been employed have GLP-1–staining neurons. Central GLP-1 ologic levels of GLP-1 in humans decrease been to use GLP-1 R agonists, including synthesis occurs almost exclusively in the food intake with increased fullness and exenatide, liraglutide, and CJC-1131, and NTS, but GLP-1Rs are widespread, found satiety in a dose-dependent fashion. DPP-IV inhibitors, those in development in the amygdala, the hypothalamic para- These effects may be mediated by delay in being vildagliptin (Novartis), sitagliptin ventricular nucleus, the NTS itself, and gastric emptying, but the relationship be- (Merck), and saxagliptin (Bristol-Myers circumventricular areas where the blood- tween gastric emptying and the appetite- Squibb). brain barrier (BBB) is attenuated with regulating functions of central GLP-1 is Exenatide, the pharmaceutical name greater potential effect of circulating not known. There is evidence that visceral given to the peptide exendin-4, has GLP-1. A number of stimuli increase cen- signals are mediated through the vagus Ͼ50% homology to GLP-1, acting as a tral GLP-1, including leptin and balloon nerve. The GLP-1-R is expressed in the GLP-1 agonist, but with glycine as the distension of the stomach, although in- vagus nerve, so that signals originating in second NH2-terminal amino acid, so that gestion of a large meal does not increase the gastrointestinal tract or portal vein it is not inactivated by DPP-IV. In three central GLP-1 levels. Acting in a fashion may be responsible for some of central 30-week studies, combination therapy similar to that of lithium chloride, GLP-1 effects of peripheral GLP-1. The extent to with sulfonylureas, with metformin, and decreases food intake, causes taste aver- which intestinal GLP-1 plays a role in sa- with both was associated with decrease in ϳ sion, decreases water intake, decreases tiety is uncertain, with D’Alessio com- HbA1c (A1C) by 1% from starting levels locomotor activity, decreases body tem- menting that DPP-IV inhibitors, which of ϳ8.5%. The proinsulin-to-insulin ratio perature, reduces gastric emptying, and may be considered to increase GLP-1 decreases with exenatide administration, activates sympathetic outflow and the hy- within the upper physiologic range, have suggesting improvement in ␤-cell func- pothalamic-pituitary-adrenal axis.
Load more

Recommended publications
  • NIDDK Recent Advances and Emerging Opportunities February
    NIDDK: 60 Years of Discovery, 1950-2010 The NIDDK was established as the National Institute of Arthritis and Metabolic Diseases in 1950 by U.S. President Harry S. Truman. Sixty years and four name changes later, one thing has never changed: the Institute’s commitment to improving health through high-quality research. In 2010, NIDDK celebrated the rich history of advances made possible through the federal investment in research in our laboratories here in Bethesda, MD, and in Phoenix, AZ, and by grantees around the U.S. and beyond. NIDDK’S SCIENTIFIC SYMPOSIUM: CELEBRATES PAST, LOOKS TO FUTURE On Tuesday, September 21, 2010, NIDDK hosted, “Unlocking the Secrets of Science: Building the Foundation for Future Advances,” a scientific symposium to highlight research advances made possible, in part, with NIDDK support. NIDDK director, Dr. Griffin Rodgers, welcomed all in attendance to what promised to be an exciting day of cutting-edge scientific presentations. Former NIDDK directors Dr. Lester B. Salans (Mount Sinai Medical School and Forest Laboratories), Dr. Phillip Gorden (NIDDK), and Dr. Allen M. Spiegel (Albert Einstein College of Medicine) chaired scientific sessions on Diabetes and Digestive and Kidney Diseases; Nutrition, Hematology, and Urology; and Endocrinology, Education, Outreach, and the NIDDK Intramural Research Program. Each session featured three presentations from distinguished scientists spanning NIDDK’s research mission. Photo: Ernie Branson Session 1: Diabetes and Digestive and Kidney Diseases C. Ronald Kahn, M.D., Insulin
    [Show full text]
  • 75 Scientific Sessions Corporate Symposia At
    75th SCIENTIFIC SESSIONS CORPORATE SYMPOSIA AT-A-GLANCE FRIDAY, JUNE 5, 2015: 8:00 a.m. – 1:45 p.m. Turning Words into Action in Type 2 Diabetes Sponsored by Institute for Medical and Nursing Education, Inc. And International Medical Press Supported by an educational grant from AstraZeneca Contact: Edwin Odoemelam Phone: +44-207-398-0608 Email: [email protected] Location: Westin Boston Waterfront, Harbor Ballroom This highly interactive workshop is organized by the Global Partnership for Effective Diabetes Management and is designed for healthcare professionals from around the globe, focusing on the need for early glycemic control to reduce diabetes-related complications, and discussion on how to overcome barriers to achieving goals safely. 6:30 p.m. – 9:30 p.m. 6:30 p.m. – 7:00 p.m. – Registration and Dinner 7:00 p.m. – 9:30 p.m. – Educational Program El Panorama Cambiante Sobre el Tratamiento de la Diabetes Tipo 2 con Insulina (Presentado en Español) Jointly sponsored by University of Texas Southwestern Medical Center and Worldwide Initiative for Diabetes Education Supported by an unrestricted educational grant from Novo Nordisk Contacts: Mark Vinciguerra, University of Texas Southwestern Medical Center Phone/Email: 214-648-4852; [email protected] Jane Savio, Worldwide Initiative for Diabetes Education Phone/Email: 212-614-4337; [email protected] Location: Westin Boston Waterfront, Harbor Ballroom Este simposio se enfocará en insulinas y nuevas tendencias en terapias de insulina, como es que están redefiniendo el cuidado de la diabetes tipo 2 hoy en día y que esperanza están aportando para hacer frente a la creciente demanda mundial debido al crecimiento de la diabetes y sus complicaciones.
    [Show full text]
  • Characterization of Insulin Receptors in Patients with the Syndromes of Insulin Resistance and Acanthosis Nigricans
    Diabetologia 18, 209-216 (1980) Diabetologia by Springer-Verlag 1980 Characterization of Insulin Receptors in Patients with the Syndromes of Insulin Resistance and Acanthosis Nigricans R. S. Bar s, M. Muggeo, C. R. Kahn, Ph. Gorden, and J. Roth 1Division of Endocrinology, University of Iowa, Iowa City, Iowa, and Diabetes Branch, NIH, Bethesda, Maryland, USA Summary. This report analyzes the in vitro charac- patients have circulating antibodies which impair teristics of ~25I-insulin binding to the monocytes of insulin receptor function. The clinical course in some nine patients with the syndromes of acanthosis nigri- of these patients [5, 6] and a detailed description and cans and insulin resistance. The 3 Type A patients characterization of the autoantibodies to the insulin (without demonstrable autoantibodies to the insulin receptor have been reported previously [7-15]. receptor) had decreased binding of insulin due to a In the present study we have analyzed in greater decreased concentration of receptors. In these detail the interaction of insulin with its receptor on patients the residual receptors demonstrated normal the circulating monocytes of nine patients with these dissociation kinetics, negative cooperativity, and syndromes (3 Type A and 6 Type B) in order to were blocked by anti-receptor antibodies in a manner elucidate further the pathogenesis of these syn- similar to normal cells. In contrast, monocytes from dromes. the 6 Type B patients (with circulating anti-receptor autoantibodies) had decreased binding of insulin due to a decrease in receptor affinity. Insulin binding to Materials and Methods monocytes of Type B patients demonstrated acceler- ated rates of dissociation with no evidence of Patients cooperative interactions among insulin receptors.
    [Show full text]
  • A FRAUD THAT SHOOK the WORLD of SCIENCE - New Yo
    A FRAUD THAT SHOOK THE WORLD OF SCIENCE - New Yo... http://query.nytimes.com/gst/fullpage.html?res=9407EEDC1139F9... HOME PAGE MY TIMES TODAY'S PAPER VIDEO MOST POPULAR TIMES TOPICS Get Home Delivery Log In Register Now Wednesday, August 27, 2008 Health WORLD U.S. N.Y. / REGION BUSINESS TECHNOLOGY SCIENCE HEALTH SPORTS OPINION ARTS STYLE TRAVEL JOBS REAL ESTATE AUTOS RESEARCH FITNESS & NUTRITION MONEY & POLICY VIEWS HEALTH GUIDE A FRAUD THAT SHOOK THE WORLD OF SCIENCE Published: November 1, 1981 E-MAIL Morton Hunt writes frequently about science and psychology; his latest book, PRINT ''The Universe Within: A New Science Explores the Human Mind,'' will be published in February by Simon & Schuster. By Morton Hunt SAVE SHARE A Junior Scientist Accuses a Senior Scientist On a bright, cold morning in early February 1980, Jeffrey Flier, a tall, mustachioed young physician, boarded a train in Boston on his way to New Haven to carry out a distinctly disagreeable professional task. He was going to conduct an ''audit'' at the Yale University School of Medicine: He would spend some hours interrogating and examining the laboratory records of an associate professor there, one of whose published research papers on insulin metabolism had been called fraudulent by another researcher. Dr. Flier - he pronounces it ''flyer'' - was well qualified for the assignment. He had trained in diabetes research at the National Institutes of Health (N.I.H.) in Bethesda, and now, though only 31, he was chief of the diabetes metabolism unit of Beth Israel Hospital in Boston and an assistant professor at the Harvard Medical School.
    [Show full text]
  • CURRICULUM VITAE the Johns Hopkins University School of Medicine Rexford S. Ahima, MD, Phd DEMOGRAPHIC and PERSONAL INFORMATION
    CURRICULUM VITAE The Johns Hopkins University School of Medicine Rexford S. Ahima, MD, PhD DEMOGRAPHIC AND PERSONAL INFORMATION Current Appointments University 2016-present Professor of Medicine, The Johns Hopkins University School of Medicine 2016-present Professor of Public Health, The Johns Hopkins University School of Medicine 2016-present Professor of Nursing, The Johns Hopkins University School of Medicine 2016-present Bloomberg Distinguished Professor of Diabetes, The Johns Hopkins University School of Medicine 2016-present Director, Division of Endocrinology, Diabetes and Metabolism, The Johns Hopkins University School of Medicine 2016-present Adjunct Professor of Medicine, University of Pennsylvania, Perelman School of Medicine, Division of Endocrinology, Diabetes and Metabolism 2016-present Leader of Johns Hopkins Diabetes Initiative 2018-present Director, Johns Hopkins/University of Maryland Diabetes Research Center Hospital 1986-1987 Houseofficer in Medicine and Surgery, Korle Bu Teaching Hospital, Accra, Ghana 1998-1999 Associate Physician, Beth Israel Deaconess Medical Center, Boston, MA 1998-1999 Attending Endocrinologist, Beth Israel Deaconess Medical Center, Boston, MA 1999-2016 Staff Endocrinologist, Hospital of the University of Pennsylvania 1999-2016 Staff Endocrinologist, Presbyterian Medical Center 2016-present Staff Endocrinologist, Johns Hopkins Hospital 2016-present Staff Endocrinologist, Johns Hopkins Bayview Medical Center Other 1999-2016 Faculty, Institute of Neurological Sciences, University of Pennsylvania
    [Show full text]
  • A1984tu04300001
    TM Cc/NUMBER 50 This Week’s Citation Classic DECEMBER 10,1984 Kahn C R, Filer I S, Bar R S, Archer I A, Gorden P, Martin M M & Roth I. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N. Engi. I. Med. 294:739-45, 1976. [Diabetes Branch, Nati. Inst. Arthritis, Metabolism, and Digestive Dis.. NIH, Bethesda, Ml) and Dept. Pediatrics, Georgetown Univ. Sch. Med.. Washington, DCI Six patients are described representing two “As the medical community recognized syndromes of insulin resistance associated our interest in diseases associated with de- with acanthosis nigricans. The Type A pa- fects in insulin action, we were gradually re- I tients are young females with virilization and have insulin resistance due to a de- ferred several patients with syndromes of ex- crease in the number of insulin receptors on treme insulin resistance—some requiring cells. The Type B patients have an autoim- thousands of units of insulin per day. These mune syndrome with autoantibodies to the were clinically challenging cases, but even insulin receptor. [The SCI® indicates that more interestingin that they provided a way this paper has been cited in over 345 publi- to test the importance of the insulin recep- cations since 1976] tor. As we had hoped, when insulin binding to its receptor was measured using circulat- ing monocytes from these patients, there C. Ronald Kahn was a marked decrease. Jeffrey Flier recog- Research Division nized the importance of the immune fea- Joslin Diabetes Center tures in some of these patients and devel- One Joslin Place oped an assay to directly measure anti-re- Boston, MA 02215 ceptor antibodies.
    [Show full text]
  • Enabling the Collaboration Experience Broad Institute of MIT
    Broad Institute of MIT & Harvard Enabling the Collaboration Experience October 17, 2011 Overview 1. What is the Broad Institute? 2. What do we do? 3. How are we organized? 4. The Collaboration Experience 5. Challenges 6. Future 2 A brief organizational history 2002: Two major research groups come 2008: “Experiment” declared a success together • Broads announce new endowment of $400 million • Whitehead/MIT Center for Genome Research • Combined $600M Current Use + Endowment Gift • Harvard Institute of Chemistry and Cell Biology 2009: Broad Institute, Inc. established 2004: Broad Institute launched • 501(c)3 formed 9/08; Operations begin 7/09 • Initial $100M gift from Broad Foundations 2010: Carlos Slim foundation provides $65M • A 10-year “experiment” in collaborative science • New initiative in genomic disease research 2004 – 2009: Broad doubles in size • 1st U.S. collaboration to receive funding • Governed by MIT-Harvard leadership • Administratively managed within MIT 2006: 7CC headquarters building opens • 250,000 sq. ft. March 2006 fully occupied 2006: Broads double initial gift to $200M • Unrestricted for Broad research and operations 2007: Creation of new Stanley Center • Founding $100M, 10-year gift from Stanley Medical Research Institute From left: Eric Lander, Susan Hockfield, Drew Faust, Eli Broad, Edythe Broad, Deval Patrick, David Baltimore 3 Governance Educational, scientific and charitable 501(c)3 corporation Members of Corporation: • MIT • Harvard • The Eli and Edythe Broad Foundation Board of Directors (currently 15): fiduciary
    [Show full text]
  • Bittersweet Breakthroughs in Diabetes Research Experts Give Metabolic
    CELEBRATING OUR TENTH YEAR NEWS Bittersweet breakthroughs in diabetes research As the number of diabetes cases worldwide what causes the cells to die and intervene, if skyrockets, progress toward understanding you can prevent the progressive deterioration, the complex disease has been painstakingly it would be a breakthrough as well,”he says. slow. But promising new research on the links In the meantime, diabetes is still largely between obesity, the metabolic syndrome and treated with insulin injections. Other drugs in diabetes could bring new treatments into the use stimulate the pancreas to make more fray, experts say. insulin, decrease the amount of glucose According to the World Health produced by the liver, increase insulin Organization, more than 176 million people sensitivity or slow down starch absorption. worldwide have diabetes—nearly 95% of Two of the newer, more promising, drugs which is non-insulin-dependent type 2 target glucagon-like peptide-1 (GLP-1). diabetes—and the number is expected to GLP-1 stimulates insulin secretion, reduces more than double in 25 years. food intake and suppresses the hormone Because diabetes is a complex, polygenic glucagon. One GLP-1 analog (Nat. Med. 9, disease, progress has been slow, but steady, 1228; 2003) is being developed by Amylin says Alan Saltiel, director of the Life Sciences Martin Dohrn/Science Photo Library Pharmaceuticals, which plans to submit a new Institute at the University of Michigan. “We sensitivity, says Jeffrey Flier, chief academic drug application to the US Food and Drug are starting to learn about the complex officer at Beth Israel Deaconness Medical Administration in mid-2004.
    [Show full text]
  • BCS Bio Final
    Opening Session BREAST CANCER IN THE DEVELOPING WORLD: MEETING THE UNFORSEEN CHALLENGE TO WOMEN, HEALTH AND EQUITY Opening Session Opening Session Dr. Felicia Knaul Director, Harvard Global Equity Initiative Associate Professor, Harvard Medical School Felicia Knaul, MA, PhD (Economics, Harvard University) is the newly- appointed director of the Harvard Global Equity Initiative and Associate Professor at the Harvard Medical School. She is also a Senior Associate with the Mexican Health Foundation, where she has collaborated with since 1994. As a result of her personal experience, she founded Cáncer de Mama: Tómatelo a Pecho (Breast Cancer: Take it to Heart) in 2007, a program that undertakes and promotes research, advocacy, awareness and early detection initiatives on breast cancer in Latin America. Her book on her life with breast cancer “Tómatelo a Pecho” was released in October. Dr. Knaul has more than 100 publications and is a member of numerous organizations, including: Consultative Council of UNICEF in Mexico; Harvard-Mexico Foundation, Mexican Council on Competitiveness; and the High Level Early Childhood Development Secretariat at the Earth Institute of Columbia University. Dr. Knaul has held senior government posts at the Ministries of Education and Social Development in Mexico and at the Department of Planning of Colombia. She has worked for the WHO, World Bank, the Inter-American Development Bank and UNICEF. Dr. Knaul is Canadian, and resides in Boston and Mexico City. She and her husband, Dr. Julio Frenk, have two children, Hannah and Mariana Havivah. BREAST CANCER IN THE DEVELOPING WORLD: MEETING THE UNFORSEEN CHALLENGE TO WOMEN, HEALTH AND EQUITY 2 Opening Session Dr.
    [Show full text]
  • Leptin in Anorexia Nervosa and Amenorrhea
    Molecular Psychiatry (1997) 2, 267–269 1997 Stockton Press All rights reserved 1359–4184/97 $12.00 EDITORIAL Leptin in anorexia nervosa and amenorrhea In this issue of Molecular Psychiatry we publish two low leptin levels are a predictor of amenorrhea in low- articles by Hebebrand et al1 and Ko¨ pp et al2 on leptin, weight women. The authors show that in their popu- the product of the OB gene, which is synthesized by lation menstruation ceased to occur when leptin levels white fat cells, and acts in various organs, including were under the range of 1.85 mgL−1. In those subjects, the brain. Low leptin levels cause increases in food leptin levels were a better predictor of amenorrhea than intake and weight gain, and high leptin levels cause a BMI, fat mass, and percent body fat. The conclusion decrease in food intake, and increases in motor from the study is that a critical level of leptin is needed activity, energy metabolism, and body temperature, to maintain menstrual function. resulting in weight loss. The leptin receptor gene that Interestingly, studies conducted in the laboratory of has been cloned encodes five or more leptin receptor Jeffrey Flier have shown that the endocrine alterations isoforms, including a form predicted to be soluble, sev- that occur during starvation, such as increased adreno- eral short forms with small intracellular domains, and corticotropic hormone (ACTH) and cortisol levels, one long form with substantial homology to the sig- which are among the biological hallmarks of anorexia naling domain of the type I cytokine receptor family nervosa, can be reversed in food-deprived animals by that utilizes the JAK/STAT pathway for signal trans- the administration of exogenous leptin.7 Based on duction.3–5 The discoveries of leptin and leptin recep- those data, we have tested the hypothesis that in tors have created a new area of investigation in endo- humans endogenous leptin levels are inversely related crinology and metabolism.
    [Show full text]
  • Correlation Between CRP, Albumin and Obesity- a Systematic Review Sumaia Radi¹, Abdulmalik Altaf ², Noura Eid³
    International Journal of Academic Scientific Research ISSN: 2272-6446 Volume 5, Issue 2 (May - June 2017), PP 25 - 46 Correlation between CRP, Albumin and obesity- a systematic review Sumaia Radi¹, Abdulmalik Altaf ², Noura Eid³ ¹ Medical Technology Department, Faculty of Applied Medical Sciences/ KAU, SA ² Department of Surgery, Faculty of Medicine/ KAU, SA ³ Clinical Nutrition Department, Faculty of Applied Medical Sciences/ KAU, SA ABSTRACT Obesity is a chronic condition characterised by an accumulation of body fat. It is rapidly becoming an emerging disease in developed and developing countries due to the increasing westernisation of societies and change in the lifestyle. The aetiology of obesity is multifactorial, with a combination of genetic and environmental factors. There are three levels of obesity management: lifestyle modification (diet, physical activity and behaviour change), pharmacotherapy and bariatric surgery. Bariatric surgery is accepted nowadays as the most effective tool in the treatment and control of morbid obesity. Several studies have shownpre- and post-operative nutritional deficiency in obese patients. Additionally, Obesity is a chronic low grade inflammation state which lead to increase in C-Reactive Protein (CRP) and many nutrient deficiencies such as Serum albumin (SA). SA has been frequently used as an index of protein status and has been shown to correlate with risk for surgical complications and mortality.Little research has linked obesity and hypoalbuminaemia. In this review, we want to see whether there is a relation between morbidly obese patients, hypoalbuminaemia and CRP. Keywords: CRP, Hypoalbuminaemia, Inflammation, Obesity, Protein. 1. Introduction Obesity is a chronic condition characterised by an accumulation of body fat [1].
    [Show full text]
  • Nutrition, Diabetes, and Human Health Saturday, June 6, 2015 | 5:30-9:15 Pm the Westin Boston Waterfront 425 Summer Street Boston, MA 02210
    EIGHTH ANNUAL GERALD J. FRIEDMAN FELLOWS SYMPOSIUM Nutrition, Diabetes, and Human Health Saturday, June 6, 2015 | 5:30-9:15 pm The Westin Boston Waterfront 425 Summer Street Boston, MA 02210 Hosted by: Gerald J. Friedman Diabetes Institute Division of Endocrinology and Metabolism Lenox Hill Hospital, North Shore – LIJ Health System, New York, NY Division of Endocrinology, Diabetes and Metabolism Tufts Medical Center, Boston, Massachusetts Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy Tufts University, Boston, Massachusetts Sponsored by the Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research Lenox Hill Hospital North Shore-LIJ Health System The Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research is a non-profit, chari- table organization dedicated to empowering scientists and clinicians focused on improving health and curing dis- ease. It was established by Gerald J. Friedman, M.D., a lifelong New Yorker who earned his Bachelor's and medical degrees from New York University,��� and returned there to teach as full professor of medicine for most of his career. After serving as commanding officer of the 222nd Station Hospital in World War II, he joined the staff of Beth Israel Medical Center in New York City, where he stayed until 1993, holding many key positions: Chief of the Gerald J Friedman Medical Intensive Care Unit, Chief of Diabetes and Metabolism, Chief of Metabolism and Endocrinology, and President of the Center's medical board. For more than 30 years, beginning in 1957, he served as the Interna- tional Medical Director for United Parcel Service.
    [Show full text]