caa a22 4500 475771095 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s001250051364 doi (NATIONALLICENCE)springer-10.1007/s001250051364 Islet amyloid polypeptide in the islets of Langerhans: friend or foe? [Elektronische Daten] [S. Gebre-Medhin, C. Olofsson, H. Mulder] Islet amyloid polypeptide (IAPP), or amylin, was originally discovered as the constituent peptide in amyloid occurring in human insulinomas and in pancreatic islets in human subjects with Type II (non-insulin-dependent) diabetes mellitus. Its normal expression in beta cells and its co-secretion with insulin in response to nutrient stimuli, suggest a metabolic function for the peptide. Specifically, IAPP has most frequently been shown to inhibit insulin secretion, implying that IAPP has a role in the regulation of islet hormone homeostasis. The physiological significance of IAPP in islets has been difficult to assess; very high IAPP concentrations are required to alter insulin secretion. Moreover, until recently, IAPP receptors have not been characterised at the molecular level, thus leaving the actual target cells for IAPP unidentified. Furthermore, in experimental diabetes in rodents, the ratio of IAPP expression to that of insulin invariably is increased. In view of the pleiotropic effects attributed to IAPP, such regulation could be both adverse and beneficial in diabetes. Metabolic characterisation of mice carrying a null mutation in the IAPP gene or which overexpress IAPP in beta cells have recently confirmed that IAPP is a physiological inhibitor of insulin secretion. Based on experiments in which IAPP-deficient mice develop a more severe form of alloxan-induced diabetes, we argue that the action of IAPP in the islets normally is beneficial for beta-cell function and survival; thus, the established up regulation of IAPP expression compared with that of insulin in experimental rodent diabetes could serve to protect islets under metabolically challenging circumstances. [Diabetologia (2000) 43: 687-695] Springer-Verlag Berlin Heidelberg, 2000 Keywords Alloxan-induced diabetes, beta-cell survival, calcitonin receptors, glucose tolerance, IAPP null mutant mice, insulin secretion, receptor-activity-modifying protein (RAMP), transgenic overexpression nationallicence Gebre-Medhin S. Department of Physiological Sciences, Division for Molecular and Cellular Physiology, Lund University, Lund, Sweden, SE aut Olofsson C. Department of Physiological Sciences, Division for Molecular and Cellular Physiology, Lund University, Lund, Sweden, SE aut Mulder H. Gifford Touchstone Center for Diabetes Research, Department of Biochemistry, Southwestern Medical Center, University of Texas at Dallas, Dallas, USA, US aut https://doi.org/10.1007/s001250051364 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051364 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gebre-Medhin S. Department of Physiological Sciences, Division for Molecular and Cellular Physiology, Lund University, Lund, Sweden, SE aut NATIONALLICENCE 700 1- Olofsson C. Department of Physiological Sciences, Division for Molecular and Cellular Physiology, Lund University, Lund, Sweden, SE aut NATIONALLICENCE 700 1- Mulder H. Gifford Touchstone Center for Diabetes Research, Department of Biochemistry, Southwestern Medical Center, University of Texas at Dallas, Dallas, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer