Is There a Role for Bioactive Lipids in the Pathobiology of Diabetes Mellitus?
Is There a Role for Bioactive Lipids in the Pathobiology of Diabetes Mellitus?
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生物活性脂质在糖尿病病理学中是否有作用？
DOI：
10.3389/fendo.2017.00182
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发表时间：
2017
影响因子：
5.2
通讯作者：
Das UN
中科院分区：
文献类型：
--
作者：
Das UN
炎症、循环内皮细胞一氧化氮(ENO)和脑源性神经营养因子(BDNF)水平降低、下丘脑神经递质(包括5-羟色胺和迷走神经张力)和胃肠激素活性改变、自由基浓度升高、生物活性脂类及其促炎和抗炎代谢产物水平失衡被认为在糖尿病(DM)中起作用。1型糖尿病(1型DM)是由于胰腺免疫细胞对未知的外源性和内源性毒素的反应，导致胰腺β细胞产生IL-6、肿瘤坏死因子-α(肿瘤坏死因子-α)和其他促炎细胞因子的增强而引起的自身免疫破坏(S)。另一方面，2型糖尿病是由于外周胰岛素抵抗增加，继而由于高脂肪和/或高热量饮食(富含饱和脂肪和反式脂肪)而导致IL-6和肿瘤坏死因子-α的产生增加。2型糖尿病还与下丘脑神经递质、eNO、BDNF、自由基、胃肠激素和迷走神经活动的产生和作用显著改变有关。因此，1型糖尿病是由于靠近β细胞的促炎细胞因子过度产生，而2型糖尿病是由于体循环中促炎细胞因子过量所致。因此，抑制促炎细胞因子过度产生的方法可能形成一种预防1型和2型糖尿病的新方法。Roux-en-Y胃旁路手术和类似的手术改善了2型糖尿病，部分是通过恢复正常：肠道激素、下丘脑神经递质、eNO、迷走神经活动、肠道微生物区系、生物活性脂类、肠道和下丘脑中脑源性神经营养因子的产生、导致胰腺β细胞重置葡萄糖刺激的胰岛素产生的细胞因子和自由基的浓度。我们最近的研究表明，生物活性脂质，如花生四烯酸、二十碳五烯酸和二十二碳六烯酸(不饱和脂肪酸)及其抗炎代谢产物：脂氧素A4、分解素、保护素和松脂，可能具有抗糖尿病作用。这些生物活性脂质具有抗炎作用，促进ENO、BDNF的产生，恢复下丘脑功能障碍，增强迷走神经张力，调节Ghrelin、瘦素和脂联素的产生和作用，并影响肠道微生物区系，这可能是其抗糖尿病作用的原因。这些证据表明，旨在选择性地将生物活性脂类输送到胰腺β细胞、肠道、肝脏和肌肉的方法可能预防1型和2型糖尿病。
Inflammation, decreased levels of circulating endothelial nitric oxide (eNO) and brain-derived neurotrophic factor (BDNF), altered activity of hypothalamic neurotransmitters (including serotonin and vagal tone) and gut hormones, increased concentrations of free radicals, and imbalance in the levels of bioactive lipids and their pro- and anti-inflammatory metabolites have been suggested to play a role in diabetes mellitus (DM). Type 1 diabetes mellitus (type 1 DM) is due to autoimmune destruction of pancreatic β cells because of enhanced production of IL-6 and tumor necrosis factor-α (TNF-α) and other pro-inflammatory cytokines released by immunocytes infiltrating the pancreas in response to unknown exogenous and endogenous toxin(s). On the other hand, type 2 DM is due to increased peripheral insulin resistance secondary to enhanced production of IL-6 and TNF-α in response to high-fat and/or calorie-rich diet (rich in saturated and trans fats). Type 2 DM is also associated with significant alterations in the production and action of hypothalamic neurotransmitters, eNO, BDNF, free radicals, gut hormones, and vagus nerve activity. Thus, type 1 DM is because of excess production of pro-inflammatory cytokines close to β cells, whereas type 2 DM is due to excess of pro-inflammatory cytokines in the systemic circulation. Hence, methods designed to suppress excess production of pro-inflammatory cytokines may form a new approach to prevent both type 1 and type 2 DM. Roux-en-Y gastric bypass and similar surgeries ameliorate type 2 DM, partly by restoring to normal: gut hormones, hypothalamic neurotransmitters, eNO, vagal activity, gut microbiota, bioactive lipids, BDNF production in the gut and hypothalamus, concentrations of cytokines and free radicals that results in resetting glucose-stimulated insulin production by pancreatic β cells. Our recent studies suggested that bioactive lipids, such as arachidonic acid, eicosapentaneoic acid, and docosahexaenoic acid (which are unsaturated fatty acids) and their anti-inflammatory metabolites: lipoxin A4, resolvins, protectins, and maresins, may have antidiabetic actions. These bioactive lipids have anti-inflammatory actions, enhance eNO, BDNF production, restore hypothalamic dysfunction, enhance vagal tone, modulate production and action of ghrelin, leptin and adiponectin, and influence gut microbiota that may explain their antidiabetic action. These pieces of evidence suggest that methods designed to selectively deliver bioactive lipids to pancreatic β cells, gut, liver, and muscle may prevent type 1 and type 2 DM.
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在脂肪组织中胰岛素耐药的表型后，捕获胰岛素抗性的表型后，追赶生长。
影响因子：
4.9
作者：
Berends, L. M.;Fernandez-Twinn, D. S.;Martin-Gronert, M. S.;Cripps, R. L.;Ozanne, S. E.
通讯作者：
Ozanne, S. E.
影响因子：
3.5
作者：
BAXTER, AG;KOULMANDA, M;MANDEL, TE
通讯作者：
MANDEL, TE
影响因子：
8.3
作者：
AUCHSCHWELK, W;KATUSIC, ZS;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM
影响因子：
5.3
作者：
Best, Aaron R.;Regehr, Wade G.
通讯作者：
Regehr, Wade G.
影响因子：
4.6
作者：
Bellemore, S. M.;Nikoopour, E.;Singh, B.
通讯作者：
Singh, B.