β Cell GHS-R Regulates Insulin Secretion and Sensitivity.
β Cell GHS-R Regulates Insulin Secretion and Sensitivity.
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β细胞GHS-R调节胰岛素的分泌和敏感性。
DOI：
10.3390/ijms22083950
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发表时间：
2021-04-11
影响因子：
5.6
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Pradhan G;Wu CS;Villarreal D;Lee JH;Han HW;Gaharwar A;Tian Y;Fu W;Guo S;Smith RG;Sun Y
生长激素促分泌素受体（GHS-R）是公认的调节食物摄入和肥胖，但其在葡萄糖稳态的作用还不清楚。本研究探讨了GHS-R在小鼠胰岛中的表达及其在血糖调节中的作用。我们使用Ghsr-IRES-tauGFP小鼠，用绿色荧光蛋白（GFP）作为GHS-R的替代物，以证明GFP与胰岛中胰岛素和胰高血糖素表达的共定位，证实GHS-R在β和α细胞中表达。然后，我们用MIP-Cre/ERT产生β细胞特异性GHSR缺失小鼠，并验证GHS-R抑制仅限于胰岛。MIP-Cre/ERT;Ghsrf/f小鼠表现出正常的能量稳态，具有相似的体重、身体组成和间接测热曲线。有趣的是，MIP-Cre/ERT;Ghsrf/f小鼠在葡萄糖稳态中表现出令人印象深刻的表型。与对照组相比，MIP-Cre/ERT;Ghsrf/f小鼠表现出较低的空腹血糖和胰岛素;在体内葡萄糖耐量试验（GTT）和葡萄糖刺激的胰岛素分泌（GSIS）试验期间减少的第一时相胰岛素分泌。MIP-Cre/ERT;Ghsrf/f小鼠的分离的胰岛在离体GSIS期间也显示胰岛素分泌减少。此外，MIP-Cre/ERT;Ghsrf/f小鼠在胰岛素耐受性试验（ITT）期间表现出改善的胰岛素敏感性。总之，我们的结果证实了GHS-R在胰腺β和α细胞中的表达; GHS-R细胞自主调节GSIS并调节全身胰岛素敏感性。总之，β细胞GHS-R是葡萄糖稳态的重要调节剂，GHS-R拮抗剂可能具有治疗2型糖尿病的潜力。
Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFP mice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in β and α cells. We then generated β-cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT;Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT;Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT;Ghsrf/f mice showed lower fasting blood glucose and insulin; reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT;Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT;Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic β and α cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, β cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.
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影响因子：
4.6
作者：
Kurashina T;Dezaki K;Yoshida M;Sukma Rita R;Ito K;Taguchi M;Miura R;Tominaga M;Ishibashi S;Kakei M;Yada T
通讯作者：
Yada T
DOI：
10.1152/ajpendo.00445.2011
发表时间：
2012-05-01
影响因子：
5.1
作者：
Chacko, Shaji K.;Haymond, Morey W.;Sunehag, Agneta L.
通讯作者：
Sunehag, Agneta L.
DOI：
10.1111/dom.13031
发表时间：
2017-09
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Aamodt KI;Powers AC
通讯作者：
Powers AC
DOI：
10.1152/ajpendo.00330.2007
发表时间：
2007-11-01
影响因子：
5.1
作者：
Anderwald-Stadler, Marietta;Krebs, Michael;Anderwald, Christian
通讯作者：
Anderwald, Christian
影响因子：
3.3
作者：
Filigheddu, Nicoletta;Gnocchi, Viola F.;Graziani, Andrea
通讯作者：
Graziani, Andrea