The in Vivo Regulation of Pulsatile Insulin Secretion
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Pulsatile Release of Bioactive Luteinizing Hormone in Prepubertal Girls: Discordance with Immunoreactive Luteinizing Hormone Pulses
003 I-399818712 104-0409$02.00/0 PEDIATRIC RESEARCH Vol. 21, No. 4, 1987 Copyright O 1987 International Pediatric Research Foundation, Inc I'rfnied in U.S. A. Pulsatile Release of Bioactive Luteinizing Hormone in Prepubertal Girls: Discordance with Immunoreactive Luteinizing Hormone Pulses EDWARD 0. REITER, DARLENE E. BIGGS, JOHANNES D. VELDHUIS, AND INESE Z. BEITINS Department of Pediatrics, Baystate Medical Center, SpringJield, Massachusetts 01 199 [E.O.R., D.E.B.]; Department of Medicine, University of Virginia Medical School, Charlottesville, Virginia 22908 [J.D.V.]; and Department qf Pediatrics of the University of Michigan Medical Center, Ann Arbor, Michigan 48109 [I.Z.B.] ABSTRACT. An assessment of pulsatile secretion of lu- the onset of puberty is an increase in the frequency, as well as teinizing hormone (LH), measured by both immunoassay amplitude, of GnRH pulses from the hypothalamus which is (I-LH) and rat interstitial cell testosterone production translated into gonadotropin secretory pulses from the pituitary. bioassay (B-LH), as well as of folicle-stimulating hormone Increased LH pulse frequency and amplitude, as measured by I- and glycoprotein hormone a-subunit was carried out in LH have been demonstrated in early pubertal children (1-4). In seven normal prepubertal and six normal premenarcheal addition, the mean I-LH levels have been shown to rise with pubertal girls. Samples were obtained at 20-min intervals advancement of puberty in both cross-sectional and longitudinal for a 6-h period. The hormone secretion profiles were studies (5, 6). analyzed by several computerized methods yielding pulse Pituitary gonadotropins are known to be heterogeneous. -
Shape of Glucose, Insulin, C-Peptide Curves During a 3-H Oral Glucose Tolerance Test: Any Relationship with the Degree of Glucose Tolerance?
Am J Physiol Regul Integr Comp Physiol 300: R941–R948, 2011. First published January 11, 2011; doi:10.1152/ajpregu.00650.2010. Shape of glucose, insulin, C-peptide curves during a 3-h oral glucose tolerance test: any relationship with the degree of glucose tolerance? Andrea Tura,1 Umberto Morbiducci,2 Stefano Sbrignadello,1 Yvonne Winhofer,3 Giovanni Pacini,1 and Alexandra Kautzky-Willer3 1Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy; 2Department of Mechanics, Politecnico di Torino, Torino, Italy; and 3Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria Submitted 29 September 2010; accepted in final form 14 January 2011 Tura A, Morbiducci U, Sbrignadello S, Winhofer Y, Pacini G, patients and the investigator. Thus, we expect the OGTT to Kautzky-Willer A. Shape of glucose, insulin, C-peptide curves during a 3-h maintain a relevant role in the study of glucose metabolism. oral glucose tolerance test: any relationship with the degree of glucose Up to now, little attention has been devoted to the possible tolerance? Am J Physiol Regul Integr Comp Physiol 300: R941–R948, 2011. information related to the shape of the concentration time First published January 11, 2011; doi:10.1152/ajpregu.00650.2010.—We courses of the OGTT variables. It is true that the results of aimed to analyze the shape of the glucose, insulin, and C-peptide curves some refined models of -cell function, such as that of the during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. -
Signature Redacted May 14,2014 Certified By
System Identification of Cortisol Secretion: Characterizing Pulsatile Dynamics OF TECHNOLOGy by Rose Taj Faghih JUN 1 0 2014 B.S., Electrical Engineering (2008) University of Maryland, College Park LIBRARIES S.M., Electrical Engineering and Computer Science (2010), Massachusetts Institute of Technology Submitted to the Department of Electrical Engineering and Computer Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY June 2014 @ Massachusetts Institute of Technology 2014. All rights reserved. Signature redacted Author ........... ............................. Department of Electrical Engineering and Computer Science Signature redacted May 14,2014 Certified by........ .................................... Emery N. Brown Edward Hood Taplin Professor of Medical Engineering Professor of Computational Neuroscience Thesis Supervisor Certified by Si onRtIIm mdRctE~d Munther A. Dahleh Professor of Electrical Engineering and Computer Science Professor of Engineering Systems Division Thesis Supervisor b Signature redacted,; A cce;pte d Uy .... ....... 4, ..... ...... .. .... S/Prdsar Leslie A. Kolodziejski Chair, Department Committee on Graduate Students System Identification of Cortisol Secretion: Characterizing Pulsatile Dynamics by Rose Taj Faghih Submitted to the Department of Electrical Engineering and Computer Science on May 14, 2014, in partial fulfillment of the requirements for the degree of Doctor of Philosophy Abstract Cortisol controls the body's metabolism and response to inflammation and stress. Cortisol is released in pulses from the adrenal glands in response to pulses of adreno- corticotropic hormone (ACTH) released from the anterior pituitary; in return, cortisol has a negative feedback effect on ACTH release. Modeling cortisol secretion and the interactions between ACTH and cortisol allows for quantifying normal and abnormal physiology and can potentially be used for diagnosis and optimal treatment of some cortisol disorders. -
An Optimization Formulation for Characterization of Pulsatile Cortisol Secretion
An optimization formulation for characterization of pulsatile cortisol secretion The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Faghih, Rose T. et al. "An optimization formulation for characterization of pulsatile cortisol secretion." Frontiers in Neuroscience 9 (August 2015): 228 © 2015 Faghih, Dahleh and Brown As Published http://dx.doi.org/10.3389/fnins.2015.00228 Publisher Frontiers Research Foundation Version Final published version Citable link http://hdl.handle.net/1721.1/112222 Terms of Use Creative Commons Attribution 4.0 International License Detailed Terms http://creativecommons.org/licenses/by/4.0/ ORIGINAL RESEARCH published: 11 August 2015 doi: 10.3389/fnins.2015.00228 An optimization formulation for characterization of pulsatile cortisol secretion Rose T. Faghih 1, 2, 3, 4*, Munther A. Dahleh 1, 4, 5, 6 and Emery N. Brown 2, 3, 7, 8 1 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA, 2 Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA, 3 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA, 4 Laboratory for Information and Decision Systems, Massachusetts Institute of Technology, Cambridge, MA, USA, 5 Engineering Systems Division, Massachusetts Institute of Technology, Cambridge, MA, USA, 6 Institute for Data, Systems, and Society, Massachusetts Institute of Technology, Cambridge, MA, USA, 7 Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA, 8 Department of Anesthesia, Harvard Medical School, Boston, MA, USA Edited by: Jason Ritt, Cortisol is released to relay information to cells to regulate metabolism and reaction Boston University, USA to stress and inflammation. -
Gonadotropin-Releasing Hormone Secretion Into Third
BIOLOGY OF REPRODUCTION 59, 676±683 (1998) Gonadotropin-Releasing Hormone Secretion into Third-Ventricle Cerebrospinal Fluid of Cattle: Correspondence with the Tonic and Surge Release of Luteinizing Hormone and Its Tonic Inhibition by Suckling and Neuropeptide Y1 O.S. Gazal,3 L.S. Leshin,4 R.L. Stanko,3 M.G. Thomas,5 D.H. Keisler,6 L.L. Anderson,7 and G.L. Williams2,3 Animal Reproduction Laboratory,3 Texas A&M University Agricultural Research Station, Beeville, Texas 78102 USDA/ARS Russell Agricultural Research Center,4 Athens, Georgia 30613 Department of Animal and Range Sciences,5 New Mexico State University, Las Cruces, New Mexico 88003 Department of Animal Science,6 University of Missouri, Columbia, Missouri 65211 Department of Animal Science,7 Iowa State University, Ames, Iowa 50011 ABSTRACT [1]. Although a transnasal, transsphenoidal approach has been described for collecting mixed hypophyseal portal and Objectives of the current studies were to characterize the cavernous sinus blood in ewes and young calves to monitor pattern of GnRH secretion in the cerebrospinal ¯uid of the bo- vine third ventricle, determine its correspondence with the tonic GnRH release [2, 3], the complex anatomical architecture and surge release of LH in ovariectomized cows, and examine of the cranium presents a signi®cant barrier to the practical the dynamics of GnRH pulse generator activity in response to application of this method in adult cattle. Additionally, known modulators of LH release (suckling; neuropeptide Y push-pull perfusion techniques have been used to obtain [NPY]). In ovariectomized cows, both tonic release patterns and median eminence perfusates in the rat [4], rabbit [5], and estradiol-induced surges of GnRH and LH were highly correlat- sheep [6]; but these methods, to our knowledge, have not ed (0.95; p , 0.01). -
SUPPLEMENTARY DATA APPENDIX 1. Limitations of Hba1c
SUPPLEMENTARY DATA APPENDIX 1. Limitations of HbA1c What is the relationship between metabolic control and HbA1c? To date, overall glycemic control, as measured by HbA1c, remains the established predictor of diabetes outcomes in persons with type 1 and type 2 diabetes, affecting micro- and macro-vascular complications and mortality. The Diabetes Control and Complications Trial (DCCT), followed by the Epidemiology of Diabetes Interventions and Complications (EDIC) study, demonstrated how elevated HbA1c contributes to complications in T1D (1). The United Kingdom Prospective Diabetes Study (UKPDS) confirmed the importance of glycemic control as well as other components of metabolic control, namely blood pressure, on health outcomes in people with diabetes (2). These studies provided the empiric data that serve as the basis for HbA1c targets recommended by most global organizations. These societies, for the most part, recommend target HbA1c levels of <7% (53 mmol/mol) for adults and <7.5% (58 mmol/mol) for children, although several organizations suggest an HbA1c target of ≤6.5% for adults (AACE) (3) as well as youth (4). All groups suggest aiming for an HbA1c as close to normal as possible without severe hypoglycemia while at the same time indicating a need to individualize glycemic targets according to patient age, duration, co-morbidities, and expected life expectancy with ‘less strict’ HbA1c targets for those less healthy (5). Despite advanced treatment tools, including newer pharmacologic agents (with many classes of oral hypoglycemic agents for T2D), various injectables including long- and short-acting insulin analogs) and advanced technologies (such as insulin pens, insulin pumps, and advanced insulin dosing algorithms for use with pumps or injection regimens), a minority of persons with diabetes, globally, achieve recommended HbA1c levels (6). -
2. Endocrine Control of the Oestrous Cycle
2. ENDOCRINE CONTROL OF THE OESTROUS CYCLE Introduction 2.1 The cyclic changes that occur in the female reproductive tract are initiated and regulated by the hypothalamic-pituitary-ovarian (HPO) axis. Although folliculogenesis occurs independently of hormonal stimulation up until the formation of early tertiary follicles, the gonadotrophins luteinising hormone (LH) and follicle stimulating hormone (FSH) are essential for the completion of follicular maturation and development of mature preovulatory (Graafian) follicles. The sites of production and key functions of the major reproductive hormones in the female rat are summarised in Table 2.1. Pituitary gonadotrophin secretion drives follicular maturation and oestrogen secretion 2.2 Levels of LH and FSH begin to increase just after dioestrus. Both hormones are secreted by the same secretory cells (gonadotrophs) in the pars distalis of the anterior pituitary (adenohypophysis). FSH stimulates development of the zona granulosa and triggers expression of LH receptors by granulosa cells. LH initiates the synthesis and secretion of androstenedione and, to a lesser extent, testosterone by the theca interna; these androgens are utilised by granulosa cells as substrates in the synthesis of oestrogen. Pituitary release of gonadotrophins thus drives follicular maturation and secretion of oestrogen during prooestrus. 2.3 Gonadotrophin secretion by the anterior pituitary is regulated by luteinising hormone-releasing hormone (LHRH), produced by the hypothalamus. LHRH is transported along the axons of hypothalamic neurones to the median eminence where it is secreted into the hypothalamic-hypophyseal portal system and transported to the anterior pituitary. The hypothalamus secretes LHRH in rhythmic pulses; this pulsatility is essential for the normal activation of gonadotrophs and subsequent release of LH and FSH. -
Closing in on the Mechanisms of Pulsatile Insulin Secretion
Diabetes Volume 67, March 2018 351 Closing in on the Mechanisms of Pulsatile Insulin Secretion Richard Bertram,1 Leslie S. Satin,2 and Arthur S. Sherman3 Diabetes 2018;67:351–359 | https://doi.org/10.2337/dbi17-0004 Insulin secretion from pancreatic islet b-cells occurs in b-cells within islets of Langerhans. Although such rhythms a pulsatile fashion, with a typical period of ∼5min.The are ubiquitous across species, we focus on mice, where most basis of this pulsatility in mouse islets has been inves- of the research on b-cell oscillations has been focused. We tigated for more than four decades, and the various theories anticipate that over the next decade much of what we now have been described as either qualitative or mathematical know about mouse islets will be tested in human islets. models. In many cases the models differ in their mech- Pulsatility in insulin secretion reflects oscillations in the anisms for rhythmogenesis, as well as other less important intracellular Ca2+ concentration of islet b-cells, which in PERSPECTIVES IN DIABETES details. In this Perspective, we describe two main classes of fl 2+ turn re ect bursting electrical activity (5). In intact islets, models: those in which oscillations in the intracellular Ca several types of oscillations are commonly observed. Slow concentration drive oscillations in metabolism, and those oscillations have periods typically between 4 and 6 min (Fig. in which intrinsic metabolic oscillations drive oscillations 1A). Fast oscillations are observed in other islets, with peri- in Ca2+ concentration and electrical activity. We then dis- ods typically less than 1 min (Fig. -
PDF-Document
Walker, JJ., Terry, JR., Tsaneva-Atanasova, KT., Armstrong, SP., McArdle, CA., & Lightman, SL. (Accepted/In press). Encoding and decoding mechanisms of pulsatile hormone secretion. http://hdl.handle.net/1983/1617 Early version, also known as pre-print Link to publication record in Explore Bristol Research PDF-document University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Encoding and decoding mechanisms of pulsatile hormone secretion Jamie J. Walker a, †, John R. Terry a, Krasimira Tsaneva-Atanasova a, Stephen P. Armstrong b, Craig A. McArdle b and Stafford L. Lightman b aBristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Bristol, UK. bHenry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. †[email protected] June 2010 Abstract Ultradian pulsatile hormone secretion underlies the activity of most neuroendocrine sys- tems, including the hypothalamo-pituitary adrenal (HPA) and gonadal (HPG) axes, and this pulsatile mode of signalling permits the encoding of information through both amplitude and frequency modulation. Thus in the HPA axis, glucocorticoid pulse ampli- tude increases in anticipation of waking, and in the HPG axis changing gonadotrophin- releasing hormone (GnRH) pulse frequency is the primary means by which the body alters its reproductive status during development. The prevalence of hormone pulsatility raises two crucial questions: how are ultradian pulses encoded (or generated) by these systems, and how are these pulses decoded (or interpreted) at their target sites? We have looked at mechanisms within the HPA axis responsible for encoding the pulsatile mode of glucocorticoid signalling that we observe in vivo. -
Pulsatile Portal Insulin Delivery Enhances Hepatic Insulin Action and Signaling Aleksey V
ORIGINAL ARTICLE Pulsatile Portal Insulin Delivery Enhances Hepatic Insulin Action and Signaling Aleksey V. Matveyenko,1 David Liuwantara,1 Tatyana Gurlo,1 David Kirakossian,1 Chiara Dalla Man,2 Claudio Cobelli,2 Morris F. White,3 Kyle D. Copps,3 Elena Volpi,4 Satoshi Fujita,4 and Peter C. Butler1 Insulin is secreted as discrete insulin secretory bursts at ;5-min Insulin secretion is regulated by the magnitude of insulin intervals into the hepatic portal vein, these pulses being attenu- pulses (12,13). Thus, hepatocytes are exposed to an oscil- ated early in the development of type 1 and type 2 diabetes mel- lating insulin concentration wave front with an amplitude of litus (T2DM). Intraportal insulin infusions (pulsatile, constant, or ;0.5–1.0 nmol/L in the fasting state and increasing to ;5.0 reproducing that in T2DM) indicated that the pattern of pulsatile nmol/L after meal ingestion (11,12). The vascular anatomy insulin secretion delivered via the portal vein is important for of hepatic sinusoids permits direct exposure of hepatocytes hepatic insulin action and, therefore, presumably for hepatic in- to these insulin oscillations. sulin signaling. To test this, we examined hepatic insulin signaling Since pulsatile insulin delivery in T1DM and T2DM is in rat livers exposed to the same three patterns of portal vein – insulin delivery by use of sequential liver biopsies in anesthetized impaired (14 16), defective pulsatile insulin delivery may rats. Intraportal delivery of insulin in a constant versus pulsatile contribute to diminished hepatic insulin signaling and he- pattern led to delayed and impaired activation of hepatic insulin patic insulin resistance in diabetes. -
By Pulsatile Gonadotropin-Releasing Hormone Injections in Male Rats Modulation by Testosterone Alfredo Garcia, Melissa Schiff, and John C
Regulation of Pituitary Gonadotropin- releasing Hormone Receptors by Pulsatile Gonadotropin-releasing Hormone Injections in Male Rats Modulation by Testosterone Alfredo Garcia, Melissa Schiff, and John C. Marshall Division of Endocrinology and Metabolism, Department of Internal Medicine, University ofMichigan, Ann Arbor, Michigan 48109 Abstract. The pattern of the gonadotropin- on the serum T concentration. With one T implant, releasing hormone (GnRH) stimulus is critically impor- increasing GnRH doses per pulse stimulated GnRH-R tant in the regulation of pituitary gonadotropin secretion in a linear manner and the maximum receptor concen- and continuous infusions down-regulate secretion while tration (703±99 fmol/mg) was seen after the 250 ng intermittent pulses maintain luteinizing hormone (LH) GnRH dose. In the presence of two T implants, GnRH- and follicle-stimulating hormone (FSH) responsiveness. R was maximal (705±45 fmol/mg) after the 25-ng dose We examined the effects of pulsatile GnRH administra- and higher doses did not increase receptors above control tion on pituitary GnRH receptors (GnRH-R) and go- values. With four T implants, GnRH doses of 5 ng nadotropin secretion in the presence of physiological induced a maximum response, 17-50 ng/pulse did not concentrations of testosterone (T) to elucidate the mech- increase GnRH-R, but receptors were again increased anisms and sites of action of GnRH and T on the by the 250-ng dose (633±86 fmol/mg). pituitary gonadotroph. After 48 h of pulsatile GnRH administration there Castrate male rats received one, two, or four testos- was no correlation between the number of GnRH-R terone (T) implants (serum T concentrations of 1.1, 2.4, and LH responses to GnRH. -
Glucose-Induced Cyclic AMP Oscillations Regulate Pulsatile Insulin Secretion" Cell Metabolism, 2008, Vol
DiVA *http://uu.diva-portal.org This is an author produced version of a paper published in Cell Metabolism. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Citation for the published paper: Dyachok, Oleg; Idevall-Hagren, Olof; Sågetorp, Jenny; Tian, Geng; Wuttke, Anne; Arrieumerlou, Cécile; Akusjärvi, Göran; Gylfe, Erik; Tengholm, Anders ”Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion" Cell metabolism, 2008, Vol. 8, Issue 1: 26-37 URL: http://dx.doi.org/10.1016/j.cmet.2008.06.003 Access to the published version may require subscription. Published with permission from: Elsevier Glucose-induced cyclic AMP oscillations regulate pulsatile insulin secretion Oleg Dyachok1,2, Olof Idevall-Hagren1, Jenny Sågetorp1, Geng Tian1, Anne Wuttke1, Cécile Arrieumerlou3, Göran Akusjärvi4, Erik Gylfe1 and Anders Tengholm1* 1Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Box 571, SE- 751 23 Uppsala, Sweden 2Department of Biophysics, Kiev T. Shevchenko National University, 01033, Kiev, Ukraine 3Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056, Basel, Switzerland 4Department of Medical Biochemistry and Microbiology, Uppsala University, Biomedical Centre, Box 582, 751 23 Uppsala Running title: Glucose-induced cAMP oscillations in β-cells *Correspondence: Anders Tengholm Department of Medical Cell Biology Uppsala University Biomedical Centre, Box 571 SE-751 23 Uppsala Sweden Phone: +46-18-4714481 Fax: +46-18-4714059 E-mail: [email protected] 1 SUMMARY Cyclic AMP (cAMP) and Ca2+ are key regulators of exocytosis in many cells, including insulin-secreting β-cells. Glucose-stimulated insulin secretion from β-cells is pulsatile and 2+ 2+ involves oscillations of the cytoplasmic Ca concentration ([Ca ]i), but little is known about the detailed kinetics of cAMP signalling.