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  • Title: NMDAR antagonists for the treatment of diabetes mellitus-Current status and future directions.
    Author: Welters A, Klüppel C, Mrugala J, Wörmeyer L, Meissner T, Mayatepek E, Heiss C, Eberhard D, Lammert E.
    Journal: Diabetes Obes Metab; 2017 Sep; 19 Suppl 1():95-106. PubMed ID: 28880473.
    Abstract:
    Diabetes mellitus is characterized by chronically elevated blood glucose levels accelerated by a progressive decline of insulin-producing β-cells in the pancreatic islets. Although medications are available to transiently adjust blood glucose to normal levels, the effects of current drugs are limited when it comes to preservation of a critical mass of functional β-cells to sustainably maintain normoglycemia. In this review, we recapitulate recent evidence on the role of pancreatic N-methyl-D-aspartate receptors (NMDARs) in β-cell physiology, and summarize effects of morphinan-based NMDAR antagonists that are beneficial for insulin secretion, glucose tolerance and islet cell survival. We further discuss NMDAR-mediated molecular pathways relevant for neuronal cell survival, which may also be important for the preservation of β-cell function and mass. Finally, we summarize the literature for evidence on the role of NMDARs in the development of diabetic long-term complications, and highlight beneficial pharmacologic aspects of NMDAR antagonists in diabetic nephropathy, retinopathy as well as neuropathy.
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