Islets of Langerhans PDF
Preview Islets of Langerhans
Md. Shahidul Islam Editor Islets of Langerhans Second Edition 1 3 Reference Islets of Langerhans Md. Shahidul Islam Editor Islets of Langerhans Second Edition With170Figuresand34Tables Editor Md.ShahidulIslam DepartmentofClinicalSciencesandEducation Sodersjukhuset,KarolinskaInstitutet Stockholm,Sweden DepartmentofInternalMedicine UppsalaUniversityHospital Uppsala,Sweden ISBN978-94-007-6685-3 ISBN978-94-007-6686-0(eBook) ISBN978-94-007-6687-7(printandelectronicbundle) DOI10.1007/978-94-007-6686-0 SpringerDordrechtHeidelbergNewYorkLondon LibraryofCongressControlNumber:2014950662 #SpringerScience+BusinessMediaDordrecht2010,2015 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped.Exemptedfromthislegalreservationarebriefexcerpts inconnectionwithreviewsorscholarlyanalysisormaterialsuppliedspecificallyforthepurposeofbeing enteredandexecutedonacomputersystem,forexclusiveusebythepurchaserofthework.Duplication ofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheCopyrightLawofthe Publisher’s location, in its current version, and permission for use must always be obtained from Springer.PermissionsforusemaybeobtainedthroughRightsLinkattheCopyrightClearanceCenter. ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) “Dedicated to the living memory of Matthias Braun, M.D., Ph.D. 1966–2013” Foreword Thetinyislets ofLangerhansreceive anextraordinary amountofattentionfroma variety of interested parties, many of whom will enthusiastically welcome publi- cation of the second edition of the “Islets of Langerhans,” ably edited by Md.ShahidulIslam,M.D.,Ph.D.,oftheKarolinskaInstitute,Stockholm,Sweden. Theamountofattentionpaidtoisletsiswelldeservedbecausethefailureoftheirβ cellstoproducesufficientamountsofinsulinresultsindiabetes,withitsclimbing prevalenceworldwideanddevastatingcomplications.Intype1diabetestheβcells arealmostcompletelydecimatedbytheviciousprocessofautoimmunity.Withthe farmorecommontype2diabetes,theinsulinresistanceassociatedwithobesityand oursedentarylifestyleislinkedtoreducedβcellmassandfunction.Thesimplest view is that the β cells die because they are stressed by overwork, resulting in reductionofinsulinsecretion,whichallowsglucoselevelstoriseenoughtocause furtherimpairmentofsecretionthroughaprocesscalledglucotoxicity.Thusthereis a loss of both β cell mass and function, resulting in the concept of decreased functionalmass.Mostpeoplewithinsulinresistanceneverdeveloptype2diabetes, which leads to the conclusion the β cell failure is the sine qua non for the developmentofthediabeticstate. Following from the above, the premise that β cell failure is the root cause of diabetesisconceptuallyverysimple,whichleadstotheconclusionthatthediabetic state should be reversed by administering insulin with injections, restoring β cell function with medication or by replenishment of the β cell deficit with transplan- tationorregeneration.Indeed,theallimportantproof-of-principlewasachievedin the1990swiththedemonstrationthatbothtypes1and2diabetescouldbereversed with islet transplantation either as isolated islets placed in the liver or as whole organpancreastransplants. Thissecondeditionof“TheIsletsofLangerhans”isverytimely,becauseinspite oftheseemingsimplicityofthebasisofdiabetesandprogresswithβcellreplace- ment, we are still too far from our goal of providing these treatments for those in need. We need to understand islets on the most basic level so that preclinical therapeuticapproachescanbeexploredandthentakentopatients.The49chapters in “The Islets of Langerhans” provide up-to-date information on a carefully selectedrangeoftopics. vii viii Foreword Important Unsolved Islet Puzzles Knowingfullwelltherearemanyopinionsaboutwhichunsolvedisletquestionsare most important, I will briefly mention a selection of issues that have captured my attention. TheisletasanorganTheanatomyofisletsis highorganizedwithitscellular arrangementsandislet-acinarportalbloodflow.Weknowthatβcellsecretionhasa majorinfluenceonglucagonsecretion,butwehavemuchtolearnabouttheother interactionsbetweenbeta,alphaanddeltacellsandhowsecretionfromallofthese influences downstream acinar cell development and maintenance. The role of the pancreaticpolypeptide(PP)cellsremainsverymuchamystery. The mystery of glucose-stimulated insulin secretion (GSIS) For years we havehadsomeunderstandingoftheso-calledK pathwayofGSIS,yetwehave ATP little understanding of the quantitatively important K -independent pathway. ATP Thisremainsamajorunsolvedprobleminβcellbiology. Finding new pharmacologic targets for insulin secretion Many of the chap- tersfocusonthecellbiologyofinsulinsecretion,andthereismuchtobelearned about these very basic facets, such is glucose and fat metabolism, ion and other transporters,mitochondrialfunction,calciumhandling,phosphorylationreactions, insulinbiosynthesisandmore.Akeyquestionishowmuchmoreinsulinsecretion canwegetoutofaβcell?Simplyput,ifthecellisdepolarizedandfullystimulated bycyclicAMP,whatapproachescanbeusedtogeneratemoreinsulinsecretion? DedifferentiationofβcellsandisletcellplasticityThephenotypeofβcellsin thediabeticstateisderangedandaccompaniedbydysfunctionalinsulinsecretion, with evidence pointing to glucotoxicity as the major driving force responsible for these changes. Restoration of normal glucose levels reverse these changes, but questions remain as to whether these β cells dedifferentiate toward a pluripotent progenitorstateorsomeotherdistinctphenotype.Thefieldisnowswirlingwiththe concept of islet cell plasticity, such as the potential alpha and delta cells being converted to β cells. There is also a big question about the alpha cell hyperplasia seenwhenglucagonactionisinhibited:whatisthesignalofalphacellgrowth? TheneedformoreβcellsTheβcelldeficiencyofdiabetescouldberestoredby regeneration of new β cells in the pancreas or by transplanting β cells from some othersource.Asdescribedinseveralchapters, thisisoneofthemain prioritiesin diabetes research. Adult human β cells replicate very slowly but there has been great progress in understanding cell cycle mechanisms, which could somehow be exploited. Exciting progress has also be made with making mature β cells from human embryonic stemcellsandfrominducedpluripotentstem cells.Therehave also been advances in exploiting the potential of exocrine multipotent progenitor cellsandinbioengineering.Porcinecellsalsoremainonthelist. Why do β cells die and how can this be prevented? We know that β cells in type 1 diabetes are killed by the immune system, and have watched impressive advances in defining the interactions among effector T cells, T regulatory cells, Bcells,andtheinnateimmunesystem.Theprocessisveryaggressiveandthereisa greatneedtocontrolitwithminimalornoimmunosuppression.TheHolyGrailis Foreword ix restoration of tolerance. An old approach receiving renewed attention is encapsu- lation of islets to protect them from immune killing. The new biomaterials and approaches are exciting but we cannot yet be confident about its eventual value. Inthecontextoftype2diabetesmuchhasbeenwrittenabouthowβcellsdie,with mechanismsreceivingthemostattentionbeingoxidativestress,endoplasmicretic- ulumstress,toxicityfromIAPPoligomers,andthegeneralconceptof“overwork.” The reality is that the death rate is very low and we have little idea about which mechanismsarethemostimportant. Ofcoursethere are manyotherimportant questions,butthissampling fits well with the contents of this valuable new edition of “The islets of Langerhans.” Itschapterscontainimportantinformationaboutthesekeyquestions,whichmake itlikelythathoursspentreadingthisbookshouldhelpourfieldconnectthecritical dotsthatwillresultinnewtreatmentsforpeoplewithdiabetes. GordonC.Weir,M.D. Co-HeadSectiononIsletCell&RegenerativeBiology DiabetesHealthandWellnessFoundationChair JoslinDiabetesCenter ProfessorofMedicine HarvardMedicalSchool
The list of books you might like
