A new view of the beta cell

Abstract

Keywords Alphacell .Betacell .Fluorescentprobe .Functional-mass .Homing .Imaging .Internalisation .IsletofLangerhansAbbreviationsDTBZ DihydrotetrabenazineGLP-1 Glucagon-like peptide 1PET Positron emission tomographyTMEM27 Transmembrane protein 27There is a current unmet need in diabetology for a directmeasure of the functional beta cell mass in patients, partly asa result of a lack of appropriate probes. In this issue ofDiabetologia, Vats and colleagues describe the generationof a new antibody raised against transmembrane protein 27(TMEM27) with promising features for use in beta cellimaging in humans [1].Diabetes mellitus is characterised by high blood glucoselevelscausedbyaninsufficientfunctionalbetacellmass,whichis determined by the actual beta cell mass and how muchinsulin the beta cells produce relative to the physiologicaldemand. Diabetes is a group of metabolic diseases withcompletely different aetiologies; there are three maintypes: type 1 diabetes is caused by autoimmune destructionof the beta cells, resulting in an absolute beta cell deficiency,whereastype2diabetesandgestationaldiabetesarecausedbyarelativebetacelldeficiencyresultingfromperipheralinsulinresistanceandinadequatebetacellfunction,whichisfollowedby loss of beta cell mass in type 2 diabetes.The beta cell mass is plastic, allowing adaptation tophysiological demand. For example, the pancreas is able toincrease the beta cell mass during pregnancy and in obesity,at least in rodents, thus compensating for the increaseddemand for insulin caused by insulin resistance. Diabetesdevelops when this mechanism fails, and it is thereforethought that drugs that improve the capacity to expand thebeta cell mass or, alternatively, prevent the loss of beta cellmass will be of great clinical importance in the treatment ofdiabetes. Evidence from mouse studies has suggested that,even after near complete loss of beta cells, the pancreas hasthe capacity to spontaneously regenerate a sufficiently largefunctional beta cell mass to become independent of insulintreatment [2]. Furthermore, measurable levels of circulatingC-peptide,as well as pancreatic insulin-positive cells,canbefound in type 1 diabetic patients, even many years after theonset of the disease [3]. This is indicative of sustainedformation of new beta cells, lending hope to the notion thatinduction of immune tolerance could offer a potential curefor type 1 diabetes, perhaps in combination with regenerativemedicine.Although beta cell mass declines in both type 1 and type 2diabetes in humans, the process is poorly understood becauseonlyindirectmeansareavailableforestimationofthebetacellmass in vivo. These are based on correlations between func-tional insulin secretion measurements and beta cell mass [4].Furthermore, establishment of the beta cell mass by mor-phometry on biopsies may be grossly misleading owing to