Mendes Ana Karla Bittencourt, Sulis Paola Miranda, Cavalari Fernanda Carvalho, Padilla Diana Patricia Rey, Aragón Marcela, Gaspar Joana Margarida, Silva Fátima Regina Mena Barreto
Departamento de Bioquímica, Núcleo de Bioeletricidade Celular (NUBIOCEL), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis- SC, Brazil.
Departamento de Bioquímica, Núcleo de Bioeletricidade Celular (NUBIOCEL), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis- SC, Brazil; Núcleo de Bioeletricidade Celular (NUBIOCEL), Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Florianópolis- SC, Brazil.
J Nutr Biochem. 2022 Jan;99:108864. doi: 10.1016/j.jnutbio.2021.108864. Epub 2021 Oct 1.
Vitamin D is associated with improvements in insulin resistance and glycemia. In this study, we investigated the short-term effect of 1α,25(OH) Vitamin D (1,25-D) and cholecalciferol (vitamin D) on the glycemia and insulin sensitivity of control and dexamethasone-induced insulin-resistance rats. Ca influx responses to 1,25-D and its role in insulin secretion were investigated in isolated pancreatic islets from control rats. In vivo, 5 d treatment with 1,25-D (i.p.) prevented insulin resistance in dexamethasone-treated rats. Treatment with 1,25-D improved the activities of hepatic enzymes, serum lipids and calcium concentrations in insulin-resistant rats. 25-D (o.g.) does not affect insulin resistance. In pancreatic islets, 1,25-D increased insulin secretion and stimulated rapid response Ca influx. The stimulatory effect of 1,25-D on Ca influx was decreased by diazoxide, apamine, thapsigargin, dantrolene, 2-APB, nifedipine, TEA, PKA, PKC, and cytoskeleton inhibitor, while it was increased by glibenclamide and N-ethylmaleimide. The stimulatory effect of 1,25-D on Ca influx involves the activation of L-type VDCC, K-ATP, K-Ca and Kv channels, which augment cytosolic calcium. These ionic changes mobilize calcium from stores and downstream activation of PKC, PKA tethering vesicle traffic and fusion at the plasma membrane for insulin secretion. This is the first study highlighting the unprecedented role of 1,25-D (short-term effect) in the regulation of glucose homeostasis and on prevention of insulin resistance. Furthermore, this study shows the intracellular β-cell signal transduction of 1,25-D through the modulation of pivotal ionic channels and proteins exhibiting a coordinated exocytosis of vesicles for insulin secretion.
维生素D与胰岛素抵抗和血糖水平的改善有关。在本研究中，我们调查了1α,25(OH)维生素D（1,25-D）和胆钙化醇（维生素D）对正常及地塞米松诱导的胰岛素抵抗大鼠血糖水平和胰岛素敏感性的短期影响。研究了正常大鼠分离的胰岛中钙内流对1,25-D的反应及其在胰岛素分泌中的作用。在体内，用1,25-D（腹腔注射）进行5天治疗可预防地塞米松处理大鼠的胰岛素抵抗。用1,25-D治疗可改善胰岛素抵抗大鼠的肝酶活性、血脂和钙浓度。25-D（口服给药）不影响胰岛素抵抗。在胰岛中，1,25-D增加胰岛素分泌并刺激快速反应性钙内流。二氮嗪、蜂毒明肽、毒胡萝卜素、丹曲林、2-氨基乙氧基二苯硼酸、硝苯地平、四乙铵、蛋白激酶A、蛋白激酶C和细胞骨架抑制剂可降低1,25-D对钙内流的刺激作用，而格列本脲和N-乙基马来酰亚胺可增强该作用。1,25-D对钙内流的刺激作用涉及L型电压依赖性钙通道、ATP敏感性钾通道、钙激活钾通道和电压门控钾通道的激活，这些通道可增加胞质钙。这些离子变化从储存部位动员钙，并在下游激活蛋白激酶C、蛋白激酶A，使囊泡运输和融合固定在质膜上以促进胰岛素分泌。这是第一项突出1,25-D（短期作用）在调节葡萄糖稳态和预防胰岛素抵抗方面前所未有的作用的研究。此外，本研究显示了1,25-D通过调节关键离子通道和蛋白质在细胞内β细胞信号转导中的作用，这些通道和蛋白质表现出囊泡协同胞吐作用以促进胰岛素分泌。
