Development and Analysis of Novel Therapeutic Targets to Improve Pancreatic β-Cell Function in Type 2 Diabetes

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  • Kaneko Yukiko K.
    Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka

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Other Title
  • 2型糖尿病による膵β細胞機能障害からの回復を目指した新規糖尿病治療標的の探索と機能解析
  • 2ガタ トウニョウビョウ ニ ヨル スイvサイボウ キノウ ショウガイ カラ ノ カイフク オ メザシタ シンキ トウニョウビョウ チリョウ ヒョウテキ ノ タンサク ト キノウ カイセキ
  • Development and Analysis of Novel Therapeutic Targets to Improve Pancreatic β-Cell Function in Type 2 Diabetes

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Pancreatic β-cell dysfunction is a major feature of type 2 diabetes. Therefore maintenance of β-cell function is essential to preventing the onset and progression of type 2 diabetes. To elucidate the mechanisms underlying the regulation of insulin secretion and β-cell survival, we particularly focused on the roles of gasotransmitters in pancreatic β-cells. Nitric oxide (NO) and hydrogen sulfide (H2S) are recognized as toxic gases. However, they are also vital physiological and pathophysiological mediators in various cell types. NO, generated from L-arginine by reactions catalyzed by NO synthases, is a well-known neurotransmitter and smooth muscle relaxation factor. In pancreatic β-cells, induction of nitric oxide synthase 2 (NOS2) by inflammatory cytokines generates a large amount of NO, which contributes to the impairment of β-cell function and induction of β-cell apoptosis, which are, in turn, involved in the development of type 1 diabetes. In contrast, a physiological level of NO, generated by constitutive NOS (cNOS), acts as a positive or negative regulator of insulin secretion and β-cell survival, depending on concentration. H2S generated from L-cysteine has been shown to play a role of neuromodulator, and this gas possesses cytoprotective properties. In pancreatic β-cells, H2S functions as a potent suppressor of insulin secretion. Furthermore, chronic exposure to high glucose induces H2S production by increasing the expression of a H2S-producing enzyme, cystathionine γ-lyase (CSE). H2S generated by CSE prevents β-cell apoptosis via an antioxidant mechanism. Here, we describe the current understanding of the function of gasotransmitters in regulating insulin secretion and pancreatic β-cell survival.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 136 (12), 1623-1629, 2016

    The Pharmaceutical Society of Japan

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