Letter to the Editor Re: Sera of Obese Type 2 Diabetic Patients Undergoing Metabolic Surgery Instead of Conventional Treatment Exert Beneficial Effects on Beta Cell Survival and Function: Results of a Randomized Clinical Study.
Letter to the Editor Re: Sera of Obese Type 2 Diabetic Patients Undergoing Metabolic Surgery Instead of Conventional Treatment Exert Beneficial Effects on Beta Cell Survival and Function: Results of a Randomized Clinical Study.
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致编辑的信回复：接受代谢手术而不是传统治疗的肥胖 2 型糖尿病患者的血清对 β 细胞存活和功能产生有益影响：随机临床研究的结果。
DOI：
10.1007/s11695-020-04665-3
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Dohm,GLynis
中科院分区：
文献类型：
--
作者：
Pories,WalterJ;Dohm,GLynis
我们祝贺Alina Constantin和她的同事[1]的主要贡献，他们记录了β细胞的培养受到肥胖2型糖尿病（T2D）患者的血清的不利影响，并且当细胞暴露于接受腹腔镜胃套管手术（LSG）治疗的类似随机患者的血清时，这些有害影响会减少。在6个月的随访中，接受LSG治疗的患者实现了血糖控制，而接受常规治疗的患者则没有。暴露于lsg处理的参与者血清中的细胞表现出(1)活力和增殖增加，(2)活性氧和p53水平降低，(3)自噬相关的SIRT1和p62/SQSTM1蛋白表达增强，(4)内皮网（ER）应激标志物转录水平显著降低，(5)胰岛素表达增强。相反，6个月的常规治疗似乎对循环氧化还原状态没有影响。此外，暴露于常规治疗患者血清中的1.1个B4细胞出现轻度内质网应激。他们得出结论：“代谢手术后改善糖尿病患者的循环因子对细胞功能和生存率有有利影响。”我们会给出一个不同的结论。根据他们出色的数据和我们的研究，代谢综合征更有可能是由于接触食物刺激了来自前肠的有毒信号。这些血源性信号限制乙酰辅酶a进入TCA循环。然后，线粒体氧化底物减少到ATP产量低于维持肌肉功能所需的水平，并且需要代偿性地增加糖酵解成乳酸。肌肉产生的乳酸引起血浆乳酸浓度升高，从而通过质量作用驱动肝脏糖异生。我们把这种现象称为“科里恶性循环”。因此，在我们的模型中，循环肠道因子是不利的，并且随着时间的推移变得更糟。这一杰出的贡献来自罗马尼亚布加勒斯特的国家糖尿病、营养和代谢疾病研究所，这是糖尿病研究的领导者，这并不奇怪。该研究所有着令人着迷的历史。它的创立是为了纪念Nicolae Paulescu，他声称他在Banting和Best之前发现了胰岛素。根据维基百科，在获奖之后，他写信给诺贝尔奖委员会，声称他首先发现了胰岛素。然而，他的优先权很快就受到了挑战。Paulescu于1916年制备了胰腺提取物，并在狗身上进行了试验，但Kleiner于1915年在狗身上进行了胰腺提取物试验，Ludwig Zuelzer于1906年也进行了胰腺提取物试验。祖尔泽还写信给诺贝尔奖委员会，要求优先考虑。所有这些早期的尝试都产生了胰腺提取物，对狗或人产生了副作用。多伦多的研究小组已经注意到他们早期提取的同样的副作用，但他们继续研究这个问题，直到他们纯化了胰岛素。然而，苏格兰格拉斯哥安德森医学院生理学教授、英国糖尿病协会副主席、国际糖尿病联合会创始成员伊恩·默里说：“人们对保罗斯科这位杰出的罗马尼亚科学家的认识不够，当多伦多团队开始他们的研究时，他已经成功地从胰腺中提取了抗糖尿病激素，并证明了它在降低糖尿病狗的高血糖方面的功效。”这是医学史的乐趣所在。
We congratulate Alina Constantin and her colleagues [1] for their major contribution documenting that cultures of beta cells are adversely affected by serum from obese subjects with type 2 diabetes (T2D) and that these harmful effects are reduced when the cells are exposed to serum from similar, randomized patients who were treated with the laparascopic gastric sleeve operation (LSG). At 6-month follow-up, patients undergoing LSG achieved glycemic control, whereas conventionally treated patients did not. Cells exposed to sera from LSG-treated participants exhibited (1) increased viability and proliferation,(2) diminished levels reactive oxygen species and p53,(3) enhanced protein expression of autophagy-related SIRT1 and p62/SQSTM1,(4) significantly decreased transcript levels of endothelial reticulum (ER) stress markers, and (5) augmented insulin expression. Conversely, the 6-month conventional therapy appeared not to impact on circulating redox status. Moreover, 1.1 B4 cells exposed to sera from conventionally treated patients experienced mild ER stress. They concluded that “circulating factors in patients with improved diabetes after metabolic surgery exerted favorable effects on beta cell function and survival.” We would offer a different conclusion. Based on their excellent data as well as our studies [2], it is more likely that the metabolic syndrome is due to toxic signaling from the foregut, stimulated by contact with food. These blood-borne signals limit entry of acetyl CoA into the TCA cycle. Mitochondrial oxidation of substrates is then reduced to a point where ATP production is below that needed to maintain muscle function and a compensatory increase in glycolysis to lactate is required. Lactate produced by muscle causes increased plasma lactate concentration, and this drives liver gluconeogenesis by mass action. We have termed this phenomenon the “vicious Cori cycle”[3]. Thus, in our model, the circulating gut factors are unfavorable and become worse with time. It is not surprising that this excellent contribution came from the National Institute for Diabetes, Nutrition and Metabolic Diseases in Bucharest, Romania, a leader in diabetes research. The Institute has a fascinating history. It was founded in honor of Nicolae Paulescu who claimed that he discovered insulin before Banting and Best. Following the award, according to Wikipedia, he wrote to the Nobel Prize committee claiming that he had discovered insulin first. However, his claims to priority were soon challenged. Paulescu prepared pancreatic extract in 1916 and tested it in dogs, but Kleiner tested pancreatic extract in dogs in 1915, as did Ludwig Zuelzer in 1906. Zuelzer also wrote to the Nobel Prize committee asserting priority. All of these earlier attempts had produced pancreatic extracts that caused side effects in dogs or humans. The Toronto team had noticed the same side effects with their earlier extracts, but they continued working on the problem until they had purified insulin. However, Ian Murray, professor of physiology at the Anderson College of Medicine in Glasgow, Scotland, vice president of the British Association of Diabetes, and a founding member of the International Diabetes Federation “Insufficient recognition has been given to Paulesco, the distinguished Roumanian scientist, who at the time when the Toronto team were commencing their research had already succeeded in extracting the antidiabetic hormone of the pancreas and proving its efficacy in reducing the hyperglycaemia in diabetic dogs.” It is what makes medical history fun.