Castex Françoise, Leroy Jeremy, Broca Christophe, Mezghenna Karima, Duranton Flore, Lavallard Vanessa, Lebreton Fanny, Gross René, Wojtusciszyn Anne, Lajoix Anne-Dominique
Biocommunication in Cardio-Metabolism (BC2M), University Montpellier, Montpellier, France.
Laboratory of Cell Therapy for Diabetes, Institute for Regenerative Medicine & Biotherapy (IRMB), University Montpellier, INSERM, University Hospital Montpellier, Montpellier, France.
J Diabetes. 2020 Jul;12(7):532-541. doi: 10.1111/1753-0407.13026. Epub 2020 Mar 6.
Due to the shortage of multi-organ donors, human pancreatic islet transplantation has now been extended to islets originating from obese subjects. In this study, our aim is to compare the respective sensitivity of human islets from lean vs obese donors to chronic high glucose or high palmitate.
Human islets were isolated from pancreases harvested from brain-dead multi-organ donors. Islets were cultured during 72 hours in the presence of moderate (16.7 mmol/L) or high (28 mmoL/L) glucose concentrations, or glucose (5.6 mmoL/L) and palmitate (0.4 mmoL/L), before measurement of their response to glucose.
We first observed a greater insulin response in islets from obese donors under both basal and high-glucose conditions, confirming their hyperresponsiveness to glucose. When islets from obese donors were cultured in the presence of moderate or high glucose concentrations, insulin response to glucose remained unchanged or was slightly reduced, as opposed to that observed in lean subjects. Moreover, culturing islets from obese donors with high palmitate also induced less reduction in insulin response to glucose than in lean subjects. This partial protection of obese islets is associated with less induction of inducible nitric oxide synthase in islets, together with a greater expression of the transcription factor forkhead box O1 (FOXO1).
Our data suggest that in addition to an increased sensitivity to glucose, islets from obese subjects can be considered as more resistant to glucose and fatty acid excursions and are thus valuable candidates for transplantation.
由于多器官供体短缺，人类胰岛移植现已扩展至来自肥胖个体的胰岛。在本研究中，我们的目的是比较瘦型与肥胖型供体的人类胰岛对慢性高血糖或高棕榈酸酯的各自敏感性。
从脑死亡多器官供体摘取的胰腺中分离人类胰岛。在测量胰岛对葡萄糖的反应之前，将胰岛在中等（16.7 mmol/L）或高（28 mmol/L）葡萄糖浓度，或葡萄糖（5.6 mmol/L）和棕榈酸酯（0.4 mmol/L）存在的条件下培养72小时。
我们首先观察到，在基础和高血糖条件下，肥胖供体的胰岛胰岛素反应更大，证实了它们对葡萄糖的高反应性。当肥胖供体的胰岛在中等或高葡萄糖浓度存在的情况下培养时，与瘦型个体中观察到的情况相反，其对葡萄糖的胰岛素反应保持不变或略有降低。此外，用高棕榈酸酯培养肥胖供体的胰岛，其对葡萄糖的胰岛素反应降低程度也比瘦型个体小。肥胖胰岛的这种部分保护作用与胰岛中诱导型一氧化氮合酶的诱导减少有关，同时转录因子叉头框O1（FOXO1）的表达增加。
我们的数据表明，除了对葡萄糖的敏感性增加外，肥胖个体的胰岛对葡萄糖和脂肪酸波动更具抗性，因此是移植的有价值候选者。
