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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells.

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 microM), S 21403, like classical sulphonylurea, induced insulin release in the absence of glucose. In contrast, at therapeutic (0.1-1.0 microM) 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 microM 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 microM S 21403. Yet, 24-h exposure of rat islets to S 21403 resulted in 30% increase in proinsulin biosynthesis at 8.3 mM glucose. Amplification by S 21403 of glucose-induced insulin secretion in diabetic GK beta-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.[1]


  1. Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells. Kaiser, N., Nesher, R., Oprescu, A., Efendic, S., Cerasi, E. Br. J. Pharmacol. (2005) [Pubmed]
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