Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance and hyperinsulinemia in early disease stages but a relative insulin insufficiency in later stages. Insulin, a peptide hormone, is produced in and secreted from pancreatic β-cells following elevated blood glucose levels. Upon its release, insulin induces the removal of excessive exogenous glucose from the bloodstream primarily by stimulating glucose uptake into insulin-dependent tissues as well as promoting hepatic glycogenesis. Given the increasing prevalence of T2DM worldwide, elucidating the underlying mechanisms and identifying the various players involved in the synthesis and exocytosis of insulin from β-cells is of utmost importance. This review summarizes our current understanding of the route insulin takes through the cell after its synthesis in the endoplasmic reticulum as well as our knowledge of the highly elaborate network that controls insulin release from the β-cell. This network harbors potential targets for anti-diabetic drugs and is regulated by signaling cascades from several endocrine systems.
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Cover Image
Cover Image
A merged immunofluorescence microscope image of meiotic chromosome spread from testes excised from wild-type male mice, stained with antibodies against phospho-gamma-H2AX (green) to detect DNA damage and Sycp3 (red) to determine the stage of progression of cells during synapsis. Cells were counter-stained with DAPI (blue). Images were visualized and taken using Zeiss AxioImager Z1 epifluorescence microscope with Zeiss AxioCam MRc5 at 63X objective (Zeiss Plan-APOCHROMAT, 63x/1.4 Oil DIC, ∞/0.17). Photo was taken by Joanna H.S. Lee and Philipp Kaldis, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore. Image kindly supplied by Philipp Kaldis. For further details see pages 2783–2798
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Molecular regulation of insulin granule biogenesis and exocytosis
Pia V. Röder, Xiuming Wong, Wanjin Hong, Weiping Han; Molecular regulation of insulin granule biogenesis and exocytosis. Biochem J 15 September 2016; 473 (18): 2737–2756. doi: https://doi.org/10.1042/BCJ20160291
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