DOCSLIB.ORG

Pancreatic Gastrin Stimulates Islet Differentiation of Transforming Growth Factor Alpha-Induced Ductular Precursor Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pancreatic Gastrin Stimulates Islet Differentiation of Transforming Growth Factor Alpha-Induced Ductular Precursor Cells Pancreatic gastrin stimulates islet differentiation of transforming growth factor alpha-induced ductular precursor cells. T C Wang, … , E V Schmidt, S J Brand J Clin Invest. 1993;92(3):1349-1356. https://doi.org/10.1172/JCI116708. Research Article Find the latest version: https://jci.me/116708/pdf Pancreatic Gastrin Stimulates Islet Differentiation of Transforming Growth Factor a-induced Ductular Precursor Cells Timothy C. Wang, * Susan Bonner-Weir, Phillip S. Oates, * MaryBeth Chulak, * Babette Simon, * Glenn T. Merlino,I Emmett V. Schmidt,11 and Stephen J. Brand* *Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; *Joslin Research Laboratory, Joslin Diabetes Center, Boston, Massachusetts 02215; ILaboratory ofMolecular Biology, National Cancer Institute, National Institutes ofHealth, Bethesda, Maryland 20892; and 'IMassachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129 Abstract mouse gestation, the protodifferentiated pancreas begins a phase of rapid growth and differentiation characterized by cy- Gastrin is transiently expressed in fetal islets during a critical todifferentiation of islet cells and a several hundredfold in- period of their development from protodifferentiated islet pre- crease in islet specific gene expression. Histologically, islet for- cursors in fetal pancreatic ducts. To examine the possible role mation (neogenesis) becomes apparent as proliferating islets of gastrin as an islet cell growth factor, postnatal islet growth budding from the pancreatic ducts. In the weeks after birth the was studied in transgenic mice which overexpress gastrin and rate of islet growth slows, with islet neogenesis becoming much TGFa in their pancreas. Overexpression of a TGFa transgene less apparent. The islets also attain a fully differentiated state causes metaplastic ductules containing numerous insulin ex- with maximal levels of insulin gene expression. Similar to pressing cells that resemble protodifferentiated precursors of many organs, the differentiated adult pancreas has reduced re- the fetal pancreas. However, islet mass of the TGFa transgenic generative potential and low levels of cell turnover, in contrast mice was not increased. Pancreatic overexpression of gastrin to the rapid proliferation seen in fetal development. from a chimeric insulin/ gastrin transgene transcribed from the As in many tissues, synergistic interactions between combi- insulin promoter markedly decreased the TGFa-stimulated in- nations of growth factors probably regulate pancreatic growth crease in pancreatic duct mass. Furthermore, pancreatic coex- and development (3). Although studies of fetal explants have pression of both gastrin and TGFa significantly increased islet identified important mesenchymal factors which stimulated mass in mice expressing both transgenes. These findings indi- pancreatic differentiation, these growth factors have not been cate that TGFa and gastrin can act synergistically to stimulate purified or structurally characterized (4). Some known regula- islet growth, although neither peptide alone is sufficient. Islet tory peptides have also been shown to stimulate pancreatic growth may possibly be stimulated through gastrin promoting growth and differentiation. EGF is a potent stimulus of ductu- the differentiation of insulin-positive cells in the TGFa-induced lar cell proliferation ( 5 ). Furthermore, both EGF and its homo- metaplastic ducts. This transgenic study suggests that islet logue TGFa are expressed in pancreatic duct and acinar cells, neogenesis can be reactivated in the ductular epithelium of the and EGF receptors are found on acinar cells and the apical adult pancreas by local expression of two growth factors, gas- surface of duct cells (6). Overexpression of TGFa, EGF, and trin and TGFa. (J. Clin. Invest. 1993. 92:1349-1356.) Key EGF receptor levels have been demonstrated in pancreatic words: pancreatic ducts * islets * gastrin * transforming growth duct neoplasms, supporting their role in stimulating pancreatic factor a proliferation. Transgenic overexpression of TGFa has distinc- Introduction tive effects on the pancreas which differ from other digestive organs (7, 8). Overexpression of TGFa in the liver and intes- The pancreatic islets develop from endodermal stem cells that tines causes hyperplasia. By contrast, TGFa overexpression in lie in the fetal ductular pancreatic epithelia, which also con- the mouse pancreas results in ductular hyperplasia and pro- tains stem cells that develop into the exocrine pancreas ( 1, 2). nounced interstitial fibrosis, without increasing the acinar cell Islet development proceeds through discrete developmental mass (9). TGFa overexpression also induces metaplastic states during fetal gestation, punctuated by dramatic transi- changes in the ductules manifest by the expression of amylase, tions. The initial period is a protodifferentiated state which is an acinar cell-specific product (8). Numerous ducts cells have characterized by the commitment of these pluripotent stem mixture of zymogen and mucin granules, suggesting that cells to the islet cell lineage, manifested by the expression of TGFa expression induces metaplasia of acinar cells into duct insulin and glucagon. These protodifferentiated cells comprise like cells (9). Thus, TGFa overexpression alters pancreatic dif- a population of committed islet precursor cells which express ferentiation by disturbing the normal balance between TGFa only low levels of islet specific gene products and lack the cyto- and other growth factors (7, 8). differentiation of mature islet cells ( 1). Around day 16 in Another peptide known to regulate pancreatic growth is cholecystokinin (CCK),' a gastrointestinal peptide hormone. Address correspondence to Stephen J. Brand, M. D., Ph. D., Gastroin- CCK stimulates proliferation of pancreatic acinar cell in vivo testinal Unit, Department of Medicine, Massachusetts General Hospi- and in vitro ( 10-12). Nevertheless, it is unlikely that CCK tal, Fruit Street, Boston, MA 02114. regulates pancreatic growth during fetal development since the Received for publication 4 January 1993 and in revised form 27 levels 'f CCK peptide expressed in fetal life are negligible ( 13 ). April 1993. The Journal of Clinical Investigation, Inc. 1. Abbreviations used in this paper: CCK, cholecystokinin; INSGAS, Volume 92, September 1993, 1349-1356 insulin/gastrin. Pancreatic Gastrin Stimulates Islet Growth 1349 However, gastrin, the homologue of CCK, is transiently ex- Northern blot hybridization assay pressed in the islets of the developing pancreas ( 13). In the For Northern analysis, total RNA was extracted from tissues by the adult, gastrin acts as a gastric hormone regulating acid secre- method of Cathala et al. (21). Samples of 20 msg of total RNA were tion, and consequently the major site of gastrin expression is resolved on a 1% agarose denaturing gel and transferred to nitrocellu- the stomach. In the fetus, however, the main site of gastrin lose. RNA blots were hybridized with 32P-labeled TGFa riboprobes or expression is the pancreatic islets ( 13). Although the role of exon II of human gastrin that did not cross-hybridize with endogenous pancreatic gastrin in islet development is undefined, some clin- mouse gastrin mRNA. ical observations suggest gastrin may influence islet growth. Peptide radioimmunoassays Hypergastrinemia, caused by gastrin-expressing islet cell tu- Gastrin. Tissues were extracted and assayed for gastrin immunoreactiv- mors and atrophic gastritis, is associated with nesidioblastosis, ity by radioimmunoassay as described previously using antibody 2604 which is characterized histologically by islet cells budding from which is specific for biologically active C terminally amidated gastrin, pancreatic ducts similar to that seen during in fetal islet devel- in a gastrin radioimmunoassay as previously described (22). Tyrosine opment (14, 15). An abnormal persistence of pancreatic gas- monoiodinated human gastrin 17 tracer was used in all assays and trin has also been documented in a case of infantile nesidioblas- synthetic human gastrin 17 was used as a standard. tosis ( 16). However, in neither circumstance was a causal rela- TGFa. Tissues were frozen in liquid nitrogen, ground to powder tionship established between the nesidioblastosis and gastrin with mortar and pestle, and subjected to acid-ethanol extraction as stimulation. Therefore, to elucidate the role of pancreatic gas- described (23). Extracts were reconstituted with water, and protein in we studies on the concentrations determined with a Coomassie blue dye binding assay trin expression islet development, report (Bio-Rad Laboratories, Richmond, CA). Aliquots from the pancreata transgenic overexpression of TGFa and gastrin in the pancreas, were tested in duplicate in a TGFa radioimmunoassay, which mea- which suggest that TGFa and gastrin regulate sequential stages sured competition with 1251 TGFa for binding to a solid-phase rabbit of islet development. antibody raised against the COOH terminus of rat TGFa (kit from BioTope, Seattle, WA). Methods Histological analysis and immunohistochemistry The pancreas was removed, weighed, similarly oriented in cassettes, Animals fixed in Bouin's solution, and embedded in paraffin. Routine 5-Mum FVB/N mice were obtained from Taconic Farms Inc. (Germantown, paraffin sections were stained with hematoxylin and eosin according to NY), and CD I mice were obtained from Charles River Laboratories, standard methods.
Load more

Recommended publications
  • Cholecystokinin Expression in the Developing and Regenerating Pancreas and Intestine
    233 Cholecystokinin expression in the developing and regenerating pancreas and intestine G Liu, S V Pakala, D Gu, T Krahl, L Mocnik and N Sarvetnick Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (Requests for offprints should be addressed to N Sarvetnick; Email: [email protected]) Abstract In developmental terms, the endocrine system of neither NOD mice continued this pattern. By contrast, in IFN- the gut nor the pancreatic islets has been characterized transgenic mice, CCK expression was suppressed from fully. Little is known about the involvement of cholecysto- birth to 3 months of age in the pancreata but not intestines. kinin (CCK), a gut hormone, involved in regulating the However, by 5 months of age, CCK expression appeared secretion of pancreatic hormones, and pancreatic growth. in the regenerating pancreatic ductal region of IFN- Here, we tracked CCK-expressing cells in the intestines transgenic mice. In the intestine, CCK expression per- and pancreata of normal mice (BALB/c), Non Obese sisted from fetus to adulthood and was not influenced Diabetic (NOD) mice and interferon (IFN)- transgenic by IFN-. Intestinal cells expressing CCK did not mice, which exhibit pancreatic regeneration, during em- co-express glucagon, suggesting that these cells are bryonic development, the postnatal period and adulthood. phenotypically distinct from CCK-expressing cells in We also questioned whether IFN- influences the expres- the pancreatic islets, and the effect of IFN- on sion of CCK. The results from embryonic day 16 showed CCK varies depending upon the cytokine’s specific that all three strains had CCK in the acinar region of microenvironment.
    [Show full text]
  • Ep 3075396 A1
    (19) TZZ¥Z¥_T (11) EP 3 075 396 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 05.10.2016 Bulletin 2016/40 A61K 48/00 (2006.01) C12N 5/10 (2006.01) A01K 67/027 (2006.01) A61K 38/46 (2006.01) (2006.01) (2015.01) (21) Application number: 16165607.9 A61K 31/713 A61K 35/39 C12N 5/071 (2010.01) C12N 15/113 (2010.01) (22) Date of filing: 10.10.2011 (84) Designated Contracting States: (72) Inventors: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB • HORNSTEIN, Eran GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO 7630243 Rehovot (IL) PL PT RO RS SE SI SK SM TR • MELKMAN-ZEHAVI, Tal 76100 Rehovot (IL) (30) Priority: 17.10.2010 US 393900 P • OREN, Roni 76100 Rehovot (IL) (62) Document number(s) of the earlier application(s) in accordance with Art. 76 EPC: (74) Representative: Dennemeyer & Associates S.A. 11779487.5 / 2 627 766 Postfach 70 04 25 81304 München (DE) (27) Previously filed application: 10.10.2011 PCT/IB2011/054446 Remarks: •Thecomplete document including Reference Tables (71) Applicant: Yeda Research and Development Co. and the Sequence Listing can be downloaded from Ltd. the EPO website 76100 Rehovot (IL) •This application was filed on 15-04-2016 as a divisional application to the application mentioned under INID code 62. (54) METHODS AND COMPOSITIONS FOR THE TREATMENT OF INSULIN-ASSOCIATED MEDICAL CONDITIONS (57) The present invention relates to a miR-24 or a pre-miR of said miR-24, or a nucleic acid sequence encoding said miR-24 or said pre-miR of said miR-24, for use in treating a condition associated with an insulin deficiency in a subject in need thereof.
    [Show full text]
  • Relevance of Endocrine Pancreas Nesidioblastosis To
    EDITORIALS plasia) rather than a continuous proliferation and differ- Relevance of Endocrine entiation of endocrine cells (19-21). Pancreas Nesidioblastosis to Note that normoglycemia can occur in various indi- viduals having a wide disparity in endocrine cell mass Hyperinsulinemic Hypoglycemia (20). Therefore, it is difficult to reconcile how a small Whereas surgery often concludes the saga of hypo- increase in p-cell mass could cause hyperinsulinemic glycemia, the pathologist has the final word. In children hypoglycemia, assuming the (3-cells are functionally and occasionally in adults, that word usually is nesidio- normal. The frequent recurrence of hypoglycemia after blastosis, a somewhat ill-defined and nebulous diag- 60-80% pancreatic resection also suggests that a factor nosis (1-6). Exactly what is nesidioblastosis? Does it other than increased (3-cell mass is involved. represent any sort of pathology at all? Because somatostatin has been shown to inhibit in- More than 30 years after the initial description of in- sulin secretion, a quantitative deficiency of 8-cells (or a fantile hypoglycemia by McQuarric (7), the pathogen- loss of cellular contacts between (S- and 8-cells) has esis of hyperinsulinism remains unclear in most cases. been incriminated as the etiology of the disease (22- Few resected glands from these hypoglycemic infants 25). Several studies have demonstrated a reduced den- show focal lesions: they either consist of a true adenoma sity of 8-cells in hypoglycemic infants. However, this exhibiting a compact ribbonlike pattern reminiscent of reduction is not present in all infants and must be in- that observed in islet cell tumors of adults or of focal terpreted with caution, because degranulation of 8-cells adenomatous hyperplasia.
    [Show full text]
  • Endocrine Pancreatic Tumors: Ultrastructure
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 1 Copyright© 1980, Institute for Clinical Science, Inc. Endocrine Pancreatic Tumors: Ultrastructure MERY KOSTIANOVSKY, M.D. Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107 ABSTRACT Endocrine pancreatic tumors are frequently multicellular and produce several hormones and peptides. A review of the basic concepts of hormone secretion, pancreatic islet cell composition and ultrastructural make-up of tumors is presented. The importance of correlating ultrastructural, immuno- cytochemical and biochemical studies of these tumors is emphasized. Introduction Morphofunctional Aspects of Pancreatic Islets During the last few years a great amount of information was accumulated regarding At the present time four different types the mechanisms of synthesis, storage and of cells have been described in the pan­ release of hormones.14,28,31 The use of ex­ creatic islets,17,33 each having a specific perimental in vitro m odels21,25,26,28 was secretory product (table I). A variety of very helpful in clarifying the participation other cells possibly exists, although of different organelles in the biosynthesis, further identification is awaited. By light cellular “packaging” and emyocytosis of microscopy, it is not possible to distin­ the secretory products. In a review, Lacy31 guish one type of cell from the other. has proposed a working model for hor­ Histochemical procedures are of help, mone secretion, describing the sim­ however, and B cells are easily stained ilarities between different endocrine with aldehyde fuchsin. The dicferent pro­ glands. Some of this information was ob­ cedures and empiric nature oi the silver tained through the studies of endocrine stain22 added confusion in the nomen­ pancreatic tumors as in the case of the clature of the cells (as seen in table I) discovery of pro-insulin in a beta cell where the same cell has been described adenoma.62 The purpose of this paper is to by different names.
    [Show full text]
  • Reference ID: 4125998
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Determine the number of vials to be reconstituted based on the patient’s These highlights do not include all the information needed to use weight and prescribed dose (2.2) ® CHIRHOSTIM safely and effectively. See full prescribing information for • ChiRhoStim® must be reconstituted with 0.9% Sodium Chloride CHIRHOSTIM®. Injection prior to administration (2.2) • See full prescribing information for complete information on exocrine ® CHIRHOSTIM (human secretin) for injection, for intravenous use test methods (2.3) Initial U.S. Approval: 2004 -------------------------RECENT MAJOR CHANGES----------------------------­ ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ Dosage and Administration (2.1) 07/2017 For injection: 16 mcg or 40 mcg of human secretin as a lyophilized powder in Contraindications, removed (4) 07/2017 single-dose vial for reconstitution (3) Warnings and Precautions (5.1, 5.2) 07/2017 -------------------------------CONTRAINDICATIONS-----------------------------­ -------------------------INDICATIONS AND USAGE----------------------------- None (4) ChiRhoStim® is a secretin class hormone indicated for stimulation of: • pancreatic secretions, including bicarbonate, to aid in the diagnosis of -----------------------WARNINGS AND PRECAUTIONS-----------------------­ exocrine pancreas dysfunction (1) • Hyporesponse to Secretin Stimulation Testing in Patients with • gastrin secretion to aid in the diagnosis of gastrinoma (1) Vagotomy, Inflammatory Bowel Disease or Receiving
    [Show full text]
  • Digestive System Physiology of the Pancreas
    Digestive System Physiology of the pancreas Dr. Hana Alzamil Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin What are the types of glands? Anatomy of pancreas Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Histology of the Pancreas Acini ◦ Exocrine ◦ 99% of gland Islets of Langerhans ◦ Endocrine ◦ 1% of gland Secretory function of pancreas Acinar and ductal cells in the exocrine pancreas form a close functional unit. Pancreatic acini secrete the pancreatic digestive enzymes. The ductal cells secrete large volumes of sodium bicarbonate solution The combined product of enzymes and sodium bicarbonate solution then flows through a long pancreatic duct Pancreatic duct joins the common hepatic duct to form hepatopancreatic ampulla The ampulla empties its content through papilla of vater which is surrounded by sphincter of oddi Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Composition of Pancreatic Juice Contains ◦ Water ◦ Sodium bicarbonate ◦ Digestive enzymes Pancreatic amylase pancreatic lipase Pancreatic nucleases Pancreatic proteases Functions of pancreatic secretion Fluid (pH from 7.6 to 9.0) ◦ acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen ◦ Neutralizes acidic gastric secretion Enzymes ◦
    [Show full text]
  • Nesidioblastosis in an Infant Rare Case Report
    Indian Journal of Medical Case Reports ISSN: 2319–3832(Online) An Open Access, Online International Journal Available at http://www.cibtech.org/jcr.htm 2020 Vol.9 (2) July-December, pp. 28-30/Swami and Lakhe Case Report NESIDIOBLASTOSIS IN AN INFANT RARE CASE REPORT *Swami R and Lakhe R Department of Pathology, Bharati Vidyapeeth (Deemed to be University) Medical College, Dhankawadi, Pune- 411043 *Author for Correspondence: [email protected] ABSTRACT Nesidioblastosis is a major cause of persistent hyperinsulinemic hypoglycemia of infancy and is caused by hypertrophy of the pancreatic endocrine islands. Recognition of this entity becomes important due to the fact that the hypoglycemia is so severe and frequent that it may lead to severe neurological damage in the infant manifesting as mental or psychomotor retardation or life-threatening event if not recognized and treated effectively in time. Here we present a case of 48 days old infant presented to pediatric department of bharati hospital with febrile seizures. Investigations showed persistent hypoglycemia with high serum insulin levels. The dota scan was suggestive of nesidioblastosis which was confirmed on final histopathology. Keywords: Nesidioblastosis and Hypoglycemia INTRODUCTION Nesidioblastosis is a major cause of persistent hyperinsulinemic hypoglycemia of infancy and is caused by hypertrophy of the pancreatic endocrine islands. The disease can be categorized histologically into diffuse and focal forms (Qin et al., 2015). Persistent hyperinsulinemic hypoglycemia (PHH) is a functional disorder caused by aberrant insulin release by pancreatic β cells (Ng, 2010). Nesidioblastosis is the major cause of PHH in infants and children, but in adults it is usually a consequence of a solitary insulinoma.
    [Show full text]
  • Normal Pancreatic Function 1. What Are the Functions of the Pancreas?
    Normal Pancreatic Function Stephen J. Pandol Cedars-Sinai Medical Center and Department of Veterans Affairs Los Angeles, California USA [email protected] Version 1.0, June 13, 2015 [DOI: 10.3998/panc.2015.17] 1. What are the functions of the This chapter presents processes underlying the functions of the exocrine pancreas with pancreas? references to how specific abnormalities of the The pancreas has both exocrine and endocrine pancreas can lead to disease states. function. This chapter is devoted to the exocrine functions of the pancreas. The exocrine function 2. Where is the pancreas located? is devoted to secretion of digestive enzymes, ions and water into the intestine of the gastrointestinal The illustration in Figure 1 demonstrates the (GI) tract. The digestive enzymes are necessary anatomical relationships between the pancreas for converting a meal into molecules that can be and organs surrounding it in the abdomen. The absorbed across the surface lining of the GI tract regions of the pancreas are the head, body, tail into the body. Of note, there are digestive and uncinate process (Figure 2). The distal end enzymes secreted by our salivary glands, of the common bile duct passes through the head stomach and surface epithelium of the GI tract of the pancreas and joins the pancreatic duct as it that also contribute to digestion of a meal. enters the intestine (Figure 2). Because the bile However, the exocrine pancreas is necessary for duct passes through the pancreas before entering most of the digestion of a meal and without it the intestine, diseases of the pancreas such as a there is a substantial loss of digestion that results cancer at the head of the pancreas or swelling in malnutrition.
    [Show full text]
  • Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: a Case Report and Brief Literature Review
    Case Report J Endocrinol Metab. 2019;9(6):199-202 Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: A Case Report and Brief Literature Review Vania Gomesa, b, Florbela Ferreiraa Abstract ders, characterized by inappropriate insulin secretion from the pancreatic β cells in the presence of low blood glucose (BG) Hyperinsulinemic hypoglycemia is characterized by inappropriate in- levels [1]. In adults, 0.5-5% of hypoglycemias are due to HH sulin secretion from the pancreatic β cells causing low blood glucose [1]. The diagnosis of hypoglycemia is based on Whipple’s triad levels. Nesidioblastosis is a very rare cause of hyperinsulinemic hypo- (symptoms, signs or both consistent with hypoglycemia; a low glycemia in adults. Medical therapy can effectively improve disease reliably measured plasma glucose concentration (< 55 mg/dL) symptoms. In 2014, a 45-year-old man presented with recurrent severe at the time of suspected hypoglycemia; resolution of symp- fasting and postprandial symptomatic hypoglycemia. The symptoms toms or signs when hypoglycemia is corrected) [2]. Hypogly- resolved after glucose ingestion. Fasting test was positive after only 4 cemia may have multiple etiologies: insulinoma, post-bariatric h but imaging methods (abdominal computerized tomography, mag- surgery, adult-onset nesidioblastosis, autoimmunity, medica- netic resonance imaging, endoscopic ultrasonography and octreotide tions, non-islet cell tumors, hormonal deficiencies, critical ill- scintigraphy) failed to identify pancreatic lesions. Hypoglycemia in ness and factitious hypoglycemia [3]. Insulinoma is the most face of endogenous hyperinsulinemia and lack of focal lesions in the common cause of endogenous HH in adults. On the contrary, pancreas in multiple imaging exams suggested the diagnosis of adult nesidioblastosis is a very rare cause of HH in this age group nesidioblastosis.
    [Show full text]
  • Adult-Onset Nesidioblastosis Causing Hypoglycemia an Important Clinical Entity and Continuing Treatment Dilemma
    PAPER Adult-Onset Nesidioblastosis Causing Hypoglycemia An Important Clinical Entity and Continuing Treatment Dilemma Ronald M. Witteles, MD; Francis H. Straus II, MD; Sonia L. Sugg, MD; Mahalakshmana Rao Koka, MD; Eduardo A. Costa, MD; Edwin L. Kaplan, MD Hypothesis: Nesidioblastosis is an important cause of insulin-dependent diabetes mellitus, pancreatic exo- adult hyperinsulinemic hypoglycemia, and control of this crine insufficiency, and need for reoperation. disorder can often be obtained with a 70% distal pancre- atectomy. Results: Of 32 adult patients who underwent surgical ex- ploration for hyperinsulinemic hypoglycemia at our insti- Design: The records of all adult patients operated on tution, 27 (84%) were found to have 1 or more insulino- for hypoglycemia between 1974 and 1999 were mas, and 5 (16%) were diagnosed with nesidioblastosis. reviewed retrospectively. Patients with the pathologic Each patient with nesidioblastosis underwent a 70% distal diagnosis of nesidioblastosis were contacted for pancreatectomy. Follow-up duration for the 5 patients follow-up (1.5-21 years) and are presented. Patients’ ranged from 1.5 to 21 years, with 3 patients (60%) asymp- results were compared with those of 36 other individu- tomatic and taking no medications, and 2 patients (40%) als with this disorder who were previously reported in experiencing some recurrences of hypoglycemia. The 2 pa- the literature. tients with recurrences are now successfully treated with a calcium channel blocker, an approach, to our knowledge, Setting: The University of Chicago Medical Center (Chi- never before reported for adult-onset nesidioblastosis. cago, Ill), a tertiary care facility. Conclusions: Nesidioblastosis is an uncommon but clini- Patients: A consecutive sample of all patients operated cally important cause of hypoglycemia in the adult popu- on for hypoglycemia.
    [Show full text]
  • Physiology of the Pancreas
    Te xt . Only in Females’ slide . Only in Males’ slides . Important Lecture . Numbers No.4 . Doctor notes . Notes and explanation “Be The Best Version Of You” 1 We recommended you to study Histology & Anatomy of pancreas first. Physiology of the pancreas Objectives: 1-Functional Anatomy. 2-Major components of pancreatic juice and their physiologic roles. 3-Cellular mechanisms of bicarbonate secretion. 4-Cellular mechanisms of enzyme secretion. 5-Activation of pancreatic enzymes. 6-Hormonal & neural regulation of pancreatic secretion. 7-Potentiation of the secretory response. 8- Pancreatic acini. 2 Functional Anatomy & Histology of the Pancreas Today we are concern about the digestive role of pancreas not the endocrine role, the endocrine part represent 95% of its Extra function, the left 5% represent the digestive part. Functional Anatomy: The pancreas, which lies parallel to and beneath the stomach is a large compound gland with most of its internal structure similar to that of the salivary glands (Look like them so they have both acinar cells and tubal cells) Islet of langerhans in the pancreas: the pancreas, in addition to its digestive functions, secretes two important hormones: Insulin (beta cells, 60%). Islet of Langerhans have different type of cells (alpha, beta and delta) and If we go and get a cross section view of the every single one of them can release a certain hormone. pancreatic tissue. We can see many acinar Glucagon (alpha cells, ~25%). cells and in the middle we have a ductal That are crucial for normal regulation of glucose, lipid, and protein metabolism. Also somatostatin is lumen. secreted by delta cells (form ~10% of islets’s cells).
    [Show full text]
  • Neuroendocrine TUMORS
    NeuroendocrinE This book provides you with five informative chapters These chapters guide the clinician through: • Diagnosing and Treating Gastroenteropancreatic Tumors, Including ICD-9 Codes TumorS • Clinical Presentations and Their Syndromes, Including ICD-9 Codes Diagnosis and Management Diagnosis A Comprehensive Guide to to Guide A Comprehensive NeuroendocrinE The remaining three chapters guide the clinician through the selection of appropriate assays, profiles, and dynamic challenge protocols for diagnosing and monitoring neuroendocrine symptoms. TumorS • Assays, Including CPT Codes A Comprehensive Guide to • Profiles, Including CPT Codes • Dynamic Challenge Protocols, Including CPT Codes Diagnosis and Management Inter Science Institute Inter Science Institute 944 West Hyde Park Boulevard Inglewood, California 90302 (800) 255-2873 (800) 421-7133 (310) 677-3322 Vinik Aaron I. Vinik, MD, PhD Eugene A. Woltering, MD Fax (310) 677-2846 www.interscienceinstitute.com Woltering Thomas M. O’Dorisio, MD Vay Liang W. Go, MD O’Dorisio Go Inter Science Institute GI Council Chairman Eugene A. Woltering, MD, FACS The James D. Rives Professor of Surgery and Neurosciences Chief of the Sections of Surgical Endocrinology and Oncology Director of Surgery Research The Louisiana State University Health Sciences Center New Orleans, Louisiana Executive Members Aaron I. Vinik, MD, PhD, FCP, MACP Professor of Medicine, Pathology and Neurobiology Director of Strelitz Diabetes Research Institute Eastern Virginia Medical School Norfolk, Virginia Vay Liang W.
    [Show full text]