Contractile Protein Expression and Phosphorylation and Contractility of Gastric Smooth Muscles from Obese Patients and Patients with Obesity and Diabetes.
Contractile Protein Expression and Phosphorylation and Contractility of Gastric Smooth Muscles from Obese Patients and Patients with Obesity and Diabetes.
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DOI：
10.1155/2018/8743874
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发表时间：
2018
影响因子：
4.3
通讯作者：
Perrino BA
中科院分区：
文献类型：
--
作者：
Li W;Sasse KC;Bayguinov Y;Ward SM;Perrino BA
摄取的食物通过不同的胃运动模式被接收、混合并研磨成食糜。糖尿病损害胃肌肉功能，但糖尿病引起胃肌肉功能障碍的机制尚不清楚。在这里，我们比较了肥胖的非糖尿病患者和糖尿病患者的胃肌中钙敏化和收缩蛋白的表达和磷酸化。我们还比较了电场刺激胆碱能运动神经元引起的自发相性收缩和收缩反应。应用毛细管电泳法和免疫组织化学方法检测γ-肌动蛋白、CPI17、pT38CPI-17、MYPT1、pT853-MYPT1、pT696-MYPT1、肌球蛋白轻链(MYL9)、肌球蛋白轻链(MYL9)、肌球蛋白轻链激酶(MYK)、蛋白磷酸酶-1δ(PP1δ)和Rho相关蛋白2(ROCK2)的表达。在糖尿病眼底肌中，Mylk、RoCK2和PP1mRNA的表达没有变化，MYPT1和CPI-17的δ表达降低，pT853/MYPT1和pT38/CPI-17的比值升高，但pT696/MYPT1的比值没有变化。糖尿病大鼠眼底肌肉中MYL9表达增加，但PS19/MYL9比值无明显变化。在糖尿病胃窦肌中，Mylk和MYL9的表达没有变化，而ROCK2、CPI-17和PP1的δ表达下降。PT38/CPI-17比值不变，而PS19/MYL9、pT853/MYPT1和pT696/MYPT1比值降低，与ROCK2表达减少一致。无论年龄、性别或糖尿病状态如何，非糖尿病患者和糖尿病患者胃底和胃窦肌的自发性时相收缩频率彼此之间没有显著差异。与非糖尿病的眼底和胃窦肌肉相比，糖尿病眼底和胃窦肌肉对电场刺激频率增加的反应倍数增加明显较低。肥胖糖尿病患者胃肌收缩反应及蛋白表达和磷酸化的改变，说明了解肥胖症患者胃肌钙敏化机制对胃运动的重要作用。
Ingested food is received, mixed, and ground into chyme by distinct gastric motility patterns. Diabetes impairs gastric muscle function, but the mechanisms underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we compared the expression and phosphorylation of Ca2+ sensitization and contractile proteins in human gastric muscles from obese nondiabetic and diabetic patients. We also compared the spontaneous phasic contractions and the contractile responses evoked by electrical field stimulation of cholinergic motor neurons. Fundus and antrum muscles were obtained from sleeve gastrectomies and were used in in vitro myobath contractile studies and for capillary electrophoresis and immunodetection of γ-actin, CPI-17, pT38-CPI-17, MYPT1, pT853-MYPT1, pT696-MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light chain kinase (MYLK), protein phosphatase-1δ (PP1δ), and Rho-associated kinase (ROCK2). In diabetic fundus muscles, MYLK, ROCK2, and PP1δ expression was unchanged; MYPT1 and CPI-17 expression was decreased; and the pT853/MYPT1 and pT38/CPI-17 ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9 expression was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus muscles. In diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but ROCK2, CPI-17, and PP1δ expression was decreased. The pT38/CPI-17 ratio was unchanged, while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were decreased, consistent with the reduced ROCK2 expression. The frequencies of spontaneous phasic contractions from nondiabetic and diabetic gastric fundus and antrum muscles did not significantly differ from each other, regardless of age, sex, or diabetic status. The fold increases in the contractions of diabetic fundus and antrum muscles in response to increased frequencies of electrical field stimulation were significantly lower compared to nondiabetic fundus and antrum muscles. The altered contractile responses and the protein expression and phosphorylation in gastric muscles of obese patients with diabetes illustrate the importance of understanding how smooth muscle Ca2+ sensitization mechanisms contribute to gastric motility.
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影响因子：
3.5
作者：
Ejskjaer, NT;Bradley, JL;Watkins, PJ
通讯作者：
Watkins, PJ
影响因子：
29.4
作者：
Grover M;Farrugia G;Lurken MS;Bernard CE;Faussone-Pellegrini MS;Smyrk TC;Parkman HP;Abell TL;Snape WJ;Hasler WL;Ünalp-Arida A;Nguyen L;Koch KL;Calles J;Lee L;Tonascia J;Hamilton FA;Pasricha PJ;NIDDK Gastroparesis Clinical Research Consortium
通讯作者：
NIDDK Gastroparesis Clinical Research Consortium
影响因子：
29.4
作者：
He, Wei-Qi;Peng, Ya-Jing;Zhu, Min-Sheng
通讯作者：
Zhu, Min-Sheng
影响因子：
29.4
作者：
Delgado-Aros, S;Cremonini, F;Camilleri, M
通讯作者：
Camilleri, M
影响因子：
5.5
作者：
Bhetwal, Bhupal P.;Sanders, Kenton M.;Perrino, Brian A.
通讯作者：
Perrino, Brian A.