11 results found
    1. Cell Biology

    PDIA1/P4HB is required for efficient proinsulin maturation and ß cell health in response to diet induced obesity

    Insook Jang et al.
    The major protein disulfide isomerase family member, PDIA1, is essential in beta cells of mice fed a high-fat diet to maintain glucose homeostasis, proinsulin maturation and organelle integrity.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    HID-1 is required for homotypic fusion of immature secretory granules during maturation

    Wen Du et al.
    HID-1 is a novel player mediating homotypic fusion of immature secretory granules.
    1. Cell Biology

    Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes

    Satoshi Ninagawa et al.
    The mechanism identified here that mediates olanzapine-induced b-cell dysfunction should be considered, along with weight gain, in mitigating adverse side effects when patients with schizophrenia are prescribed olanzapine.
    1. Developmental Biology

    Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

    Jonghyeob Lee et al.
    Cells from the human pancreatic duct can be grown in culture and triggered to become insulin-producing cells, which could potentially be transplanted into patients with diabetes.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress

    Mable Lam et al.
    Death receptor 5 can directly sense misfolded proteins downstream of the endoplasmic reticulum to provide a quality control mechanism that executes apoptosis and prevents further production of misfolded proteins.
    1. Cell Biology
    2. Genetics and Genomics

    Inhibition of mTORC1 by ER stress impairs neonatal β-cell expansion and predisposes to diabetes in the Akita mouse

    Yael Riahi et al.
    mTORC1 inhibition by perinatal ER stress induces beta-cell growth arrest with subsequent development of diabetes.
    1. Stem Cells and Regenerative Medicine

    Insulin mutations impair beta-cell development in a patient-derived iPSC model of neonatal diabetes

    Diego Balboa et al.
    Mutations causing proinsulin misfolding trigger unfolded protein response and lead to impaired proliferation and reduced mTORC1 signalling of developing beta-cells in a patient-derived induced pluripotent stem cell disease model.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    An unfolded protein-induced conformational switch activates mammalian IRE1

    G Elif Karagöz et al.
    ER-stress sensing mechanism of the unfolded protein response sensor/transducer IRE1 is conserved from yeast to mammals, where in mammals, unfolded protein binding to IRE1's ER lumenal domain is coupled to its oligomerization and activation through an allosteric conformational change.
    1. Cell Biology

    Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion

    Caroline Lekszas et al.
    The first human TANGO1-associated syndromal disease manifests as impaired collagen secretion, highlighting the importance of TANGO1 in human pathophysiology.
    1. Cell Biology

    Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2

    Alex J B Kreutzberger et al.
    Insulin secreting cells harbor distinct subpopulations of insulin granules and loss of one or the other correlates strongly with secretory deficiencies characterizing type-1 or type-2 diabetes.

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