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• W2054328989 abstract "S 21403 (mitiglinide) is a new drug for type 2 diabetes mellitus (T2DM). Its action on insulin release and biosynthesis was investigated in several experimental systems utilizing pancreas from normal and T2DM animals. At high concentrations (10 μ M ), S 21403, like classical sulphonylurea, induced insulin release in the absence of glucose. In contrast, at therapeutic (0.1–1.0 μ M ) concentrations, S 21403 amplified insulin secretion glucose dose‐dependently and with similar magnitude in normal and diabetic GK rat islets. In perfused GK rat pancreas, S 21403 induced normal kinetics of insulin secretion including first‐phase response. The effect of S 21403 was strongly modulated by physiological factors. Thus, 0.1 μ M adrenaline inhibited S 21403‐induced insulin release. There was marked synergism between S 21403 and arginine in GK rat islets, combination of the two normalizing insulin secretion. In primary islet cultures from normal rats or prediabetic Psammomys obesus , prolonged exposure to S 21403 did not induce further depletion of insulin stores under normal or ‘glucotoxic’ conditions. Proinsulin biosynthesis was not affected by 2‐h exposure of rat or prediabetic P. obesus islets to 1 μ M S 21403. Yet, 24‐h exposure of rat islets to S 21403 resulted in 30% increase in proinsulin biosynthesis at 8.3 m M glucose. Amplification by S 21403 of glucose‐induced insulin secretion in diabetic GK β ‐cells with restoration of first‐phase response, a strong synergistic interaction with arginine and marked inhibition by adrenaline, make it a prime candidate for successful oral antidiabetic agent. British Journal of Pharmacology (2005) 146 , 872–881. doi: 10.1038/sj.bjp.0706374" @default.
• W2054328989 created "2016-06-24" @default.
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• W2054328989 date "2005-11-01" @default.
• W2054328989 modified "2023-10-17" @default.
• W2054328989 title "Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic<i>β-</i>cells" @default.
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• W2054328989 doi "https://doi.org/10.1038/sj.bjp.0706374" @default.
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