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      The pancreatic beta cell surface proteome

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          Abstract

          The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00125-012-2531-3) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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          Most cited references79

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          Serotonin Regulates Pancreatic β-Cell Mass during Pregnancy

          During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing β-cells1–3. However, the exact mechanisms by which the lactogenic hormones drive β-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive β-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in β-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked β-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gαq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gαi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked β-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking β-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes4.
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            Autonomic regulation of islet hormone secretion--implications for health and disease.

            B. Ahrén (2000)
            The pancreatic islets are richly innervated by parasympathetic, sympathetic and sensory nerves. Several different neurotransmitters are stored within the terminals of these nerves, both the classical neurotransmitters, acetylcholine and noradrenaline, and several neuropeptides. The neuropeptides, vasoactive intestinal polypeptide, pituitary adenlyate cyclase activating polypeptide and gastrin releasing peptide are constituents of the parasympathetic nerves, whereas the neuropeptides galanin and neuropeptide Y are localised to sympathetic nerve terminals. Furthermore, the neuropeptide calcitonin gene-related peptide is localised to sensory nerves and cholecystokinin is also an islet neuropeptide, although the nature of the cholecystokinin nerves is not established. Stimulation of the autonomic nerves and treatment with neurotransmitters affect islet hormone secretion. Thus, insulin secretion is stimulated by parasympathetic nerves or their neurotransmitters and inhibited by sympathetic nerves or their neurotransmitters. The islet autonomic nerves seem to be of physiological importance in mediating the cephalic phase of insulin secretion, in synchronising the islets to function as a unit allowing oscillations of islet hormone secretion, and in optimising islet hormone secretion during metabolic stress, e.g. hypoglycaemia and neuroglycopenia. The autonomic nerves could also be involved in the islet adaptation to insulin resistance with possible implication for the development of glucose intolerance and Type II (non-insulin-dependent) diabetes mellitus. It is concluded that islet innervation, through the contribution of all branches of the autonomic nerves and several different neurotransmitters is of importance both for the physiology and pathophysiology of the islets.
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              Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans.

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                Author and article information

                Contributors
                stoffel@imsb.biol.ethz.ch
                Journal
                Diabetologia
                Diabetologia
                Diabetologia
                Springer-Verlag (Berlin/Heidelberg )
                0012-186X
                1432-0428
                31 March 2012
                31 March 2012
                July 2012
                : 55
                : 7
                : 1877-1889
                Affiliations
                [1 ]Institute of Molecular Systems Biology, HPT E73, ETH Zurich, Wolfgang-Pauli-Str. 16, 8093 Zurich, Switzerland
                [2 ]Competence Center for Systems Physiology and Metabolic Diseases, ETH Zurich, Zurich, Switzerland
                [3 ]Faculty of Medicine, University of Zurich, Zurich, Switzerland
                Article
                2531
                10.1007/s00125-012-2531-3
                3369137
                22460761
                cfd3d012-933a-4946-a8bf-03039d635b5b
                © The Author(s) 2012
                History
                : 24 October 2011
                : 30 January 2012
                Categories
                Review
                Custom metadata
                © Springer-Verlag 2012

                Endocrinology & Diabetes
                secretome,pancreatic beta cell,review,sheddome,surface proteome,islet,biomarker,proteomics

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