Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
Nutrients. 2018 Jan 26;10(2):127. doi: 10.3390/nu10020127.
Isosteviol (ISV), a diterpene molecule, is an isomer of the backbone structure of a group of substances with proven antidiabetic capabilities. The aim of this study was to investigate if ISV elicits dynamic insulin release from pancreatic islets and concomitantly is able to ameliorate gluco-, lipo-, and aminoacidotoxicity in clonal β-cell line (INS-1E) in relation to cell viability and insulin secretion. Isolated mice islets placed into perifusion chambers were perifused with 3.3 mM and 16.7 mM glucose with/without 10 M ISV. INS-1E cells were incubated for 72 h with either 30 mM glucose, 1 mM palmitate or 10 mM leucine with or without 10 M ISV. Cell viability was evaluated with a Cytotoxic Fluoro-test and insulin secretion was measured in Krebs-Ringer Buffer at 3.3 mM and 16.7 mM glucose. In the presence of 3.3 mM glucose, 10 M ISV did not change basal insulin secretion from perifused islets. However, at a high glucose level of 16.7 mM, 10 M ISV elicited a 2.5-fold increase (-ISV: 109.92 ± 18.64 ng/mL vs. +ISV: 280.15 ± 34.97 ng/mL; < 0.01). After 72 h gluco-, lipo-, or aminoacidotoxicity in INS-1E cells, ISV treatment did not significantly affect cell viability (glucotoxicity, -ISV: 19.23 ± 0.83%, +ISV: 18.41 ± 0.90%; lipotoxicity, -ISV: 70.46 ± 3.15%, +ISV: 65.38 ± 2.81%; aminoacidotoxicity: -ISV: 8.12 ± 0.63%; +ISV: 7.75 ± 0.38%, all nonsignificant). ISV did not improve impaired insulin secretion (glucotoxicity, -ISV: 52.22 ± 2.90 ng/mL, +ISV: 47.24 ± 3.61 ng/mL; lipotoxicity, -ISV: 19.94 ± 4.10 ng/mL, +ISV: 22.12 ± 3.94 ng/mL; aminoacidotoxicity: -ISV: 32.13 ± 1.00 ng/mL; +ISV: 30.61 ± 1.54 ng/mL, all nonsignificant). In conclusion, ISV acutely stimulates insulin secretion at high but not at low glucose concentrations. However, ISV did not counteract cell viability or cell dysfunction during gluco-, lipo-, or aminoacidotoxicity in INS-1E cells.
异甜菊醇（ISV）是一种二萜分子，是一组具有证明的抗糖尿病能力的物质的骨干结构的异构体。本研究的目的是研究 ISV 是否从胰岛中引发动态胰岛素释放，并同时改善克隆β细胞系（INS-1E）中的葡萄糖、脂肪和氨基酸毒性，与细胞活力和胰岛素分泌有关。将分离的小鼠胰岛置于灌注室中，用 3.3 mM 和 16.7 mM 葡萄糖灌注，有/无 10 M ISV。将 INS-1E 细胞在 30 mM 葡萄糖、1 mM 棕榈酸或 10 mM 亮氨酸中孵育 72 小时，有/无 10 M ISV。用细胞毒性荧光测试评估细胞活力，并用 Krebs-Ringer 缓冲液在 3.3 mM 和 16.7 mM 葡萄糖下测量胰岛素分泌。在 3.3 mM 葡萄糖存在下，10 M ISV 不会改变灌注胰岛的基础胰岛素分泌。然而，在高葡萄糖水平 16.7 mM 时，10 M ISV 引起 2.5 倍的增加（-ISV：109.92 ± 18.64 ng/mL 对 +ISV：280.15 ± 34.97 ng/mL； < 0.01）。在 INS-1E 细胞中经过 72 小时的葡萄糖、脂肪或氨基酸毒性后，ISV 处理并未显著影响细胞活力（葡萄糖毒性，-ISV：19.23 ± 0.83%，+ISV：18.41 ± 0.90%；脂肪毒性，-ISV：70.46 ± 3.15%，+ISV：65.38 ± 2.81%；氨基酸毒性：-ISV：8.12 ± 0.63%，+ISV：7.75 ± 0.38%，均无显著性）。ISV 并未改善受损的胰岛素分泌（葡萄糖毒性，-ISV：52.22 ± 2.90 ng/mL，+ISV：47.24 ± 3.61 ng/mL；脂肪毒性，-ISV：19.94 ± 4.10 ng/mL，+ISV：22.12 ± 3.94 ng/mL；氨基酸毒性：-ISV：32.13 ± 1.00 ng/mL，+ISV：30.61 ± 1.54 ng/mL，均无显著性）。总之，ISV 在高葡萄糖浓度而非低葡萄糖浓度下急性刺激胰岛素分泌。然而，在 INS-1E 细胞的葡萄糖、脂肪或氨基酸毒性期间，ISV 并未抵抗细胞活力或细胞功能障碍。
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