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  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 15 ( 2019-07-28), p. 3699-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 15 ( 2019-07-28), p. 3699-
    Abstract: To date, type 2 diabetes is considered to be a “bi-hormonal disorder” rather than an “insulin-centric disorder,” suggesting that glucagon is as important as insulin. Although glucagon increases hepatic glucose production and blood glucose levels, paradoxical glucagon hypersecretion is observed in diabetes. Recently, insulin resistance in pancreatic α cells has been proposed to be associated with glucagon dysregulation. Moreover, cell autonomous dysfunction of α cells is involved in the etiology of diabetes. In this review, we summarize the current knowledge about the physiological and pathological roles of glucagon.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Metabolites Vol. 11, No. 4 ( 2021-04-02), p. 218-
    In: Metabolites, MDPI AG, Vol. 11, No. 4 ( 2021-04-02), p. 218-
    Abstract: Type 2 diabetes is caused by impaired insulin secretion and/or insulin resistance. Loss of pancreatic β-cell mass detected in human diabetic patients has been considered to be a major cause of impaired insulin secretion. Additionally, apoptosis is found in pancreatic β-cells; β-cell mass loss is induced when cell death exceeds proliferation. Recently, however, β-cell dedifferentiation to pancreatic endocrine progenitor cells and β-cell transdifferentiation to α-cell was reported in human islets, which led to a new underlying molecular mechanism. Hyperglycemia inhibits nuclear translocation and expression of forkhead box-O1 (FoxO1) and induces the expression of neurogenin-3 (Ngn3), which is required for the development and maintenance of pancreatic endocrine progenitor cells. This new hypothesis (Foxology) is attracting attention because it explains molecular mechanism(s) underlying β-cell plasticity. The lineage tracing technique revealed that the contribution of dedifferentiation is higher than that of β-cell apoptosis retaining to β-cell mass loss. In addition, islet cells transdifferentiate each other, such as transdifferentiation of pancreatic β-cell to α-cell and vice versa. Islet cells can exhibit plasticity, and they may have the ability to redifferentiate into any cell type. This review describes recent findings in the dedifferentiation and transdifferentiation of β-cells. We outline novel treatment(s) for diabetes targeting islet cell plasticity.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662251-8
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  • 3
    Online Resource
    Online Resource
    Medliber Publishing Group ; 2022
    In:  International Journal of Clinical Investigation and Case Reports Vol. 01, No. 03 ( 2022), p. 67-73
    In: International Journal of Clinical Investigation and Case Reports, Medliber Publishing Group, Vol. 01, No. 03 ( 2022), p. 67-73
    Abstract: The etiology of type 2 diabetes has long been centered on insulin. Recently, however, glucagon has been attracting attention. It has been reported that glucagon receptor or pancreatic α cell-deficient mice do not deteriorate glucose intolerance after pancreatic beta cells are destroyed with streptozotocin and insulin secretion is depleted. This suggests that glucagon and glucagon receptors are crucial for glucose intolerance in diabetes mellitus, and the elucidation of glucagon signaling is still awaited. This review will begin with an overview of the history of glucagon. In the nearly 100 years since the discovery of glucagon, it has become clear that glucagon plays a role in blood glucose in type 2 diabetes as much or more than insulin. This is due in large part to the advent of the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) method, which allows accurate measurement of glucagon by using N- and C-terminal antibodies. Next, the mechanism of action of glucagon on blood glucose levels will be outlined. Glucagon increases blood glucose levels by enhancing gluconeogenesis and glycogenolysis. Glucagon also enhances lipolysis, which indirectly contributes to weight loss and improved blood glucose levels. Recently, mice with defective or decreased glucagon secretion have been developed, and the effects of glucagon are becoming clearer in vivo. Mice with elevated glucagon secretion have also appeared, and their glucose tolerance improvement through lipolysis and weight loss is also attracting attention. Research on glucagon is not limited to animal experiments but has already reached the stage of clinical application. Drugs that suppress glucagon have side effects such as liver damage, but they are effective in improving blood glucose. Drugs that increase glucagon also have hypoglycemic effects resulting from weight loss. Thus, glucagon has undergone a dizzying evolution over the past decade. The day may soon come when drugs that target glucagon will dominate diabetes treatment.
    Type of Medium: Online Resource
    URL: Issue
    Language: Unknown
    Publisher: Medliber Publishing Group
    Publication Date: 2022
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  • 4
    In: The Journal of Nutritional Biochemistry, Elsevier BV, Vol. 97 ( 2021-11), p. 108811-
    Type of Medium: Online Resource
    ISSN: 0955-2863
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1483155-7
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  • 5
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 7 ( 2022-04-04), p. 4003-
    Abstract: The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine–threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkcδ in glucagon secretion from pancreatic α-cells. Glucagon secretions were investigated in Pkcδ-knockdown InR1G9 cells and pancreatic α-cell-specific Pkcδ-knockout (αPkcδKO) mice. Knockdown of Pkcδ in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, we showed that arginine increased Pkcδ phosphorylation at Thr505, which is critical for Pkcδ activation. Interestingly, the knockdown of Pkcδ in InR1G9 cells reduced arginine-induced glucagon secretion. Moreover, arginine-induced glucagon secretions were decreased in αPkcδKO mice and islets from αPkcδKO mice. Pkcδ is essential for arginine-induced glucagon secretion in pancreatic α-cells. Therefore, this study may contribute to the elucidation of the molecular mechanism of amino acid-induced glucagon secretion and the development of novel antidiabetic drugs targeting Pkcδ and glucagon.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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