Wang Jin-yan, Wang Li-hua, Wei Liang-zhou, Wu Jun, Wei Ning, Kong Xin-juan, Tian Zi-bin
Department of Gastroenterology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
Zhonghua Yi Xue Za Zhi. 2010 Apr 27;90(16):1137-40.
To investigate the association of gastric emptying with ghrelin, obestatin and GHSR, GPR-39 in hypothalamus of diabetic rats.
Sixty Wistar rats were randomly divided into three groups: a normal control group (NC, n = 20), a diabetes mellitus group (DM, n = 20) induced by intraperitoneal injection of streptozotocin (STZ) and an insulin treated group (INS, n = 20). After two and six weeks of STZ injection, gastric emptying was measured by intragastric administration of phenol red, ghrelin and obestatin in hypothalamus measured by ELISA (enzyme-linked immunosorbent assay) and GHSR and GPR-39 by RT-PCR (reverse transcription-polymerase chain reaction).
After two weeks of STZ injection, gastric emptying (%) (74 +/- 8, 40 +/- 5), ghrelin level(ng/g) (52 +/- 9, 51 +/- 7) and ratio of ghrelin/obestatin (3.8 +/- 1.0, 2.8 +/- 1.0) increased significantly in DM and INS groups compared to those in NC group [32% +/- 7%, (39 +/- 11) ng/g, 2.1 +/- 0.8, all P < 0.05]. Obestatin level(ng/g) (14.2 +/- 2.0) of hypothesis decreased significantly in DM group as compared to those in NC group (21.7 +/- 4.7) while GHSR/beta-actin increased significantly (1.26 +/- 0.46 vs 0.77 +/- 0.21, P < 0.05). Gastric emptying was positively correlated with ghrelin, ghrelin/obestatin and GHSR/beta-actin of hypothalamus (r = 0.49; r = 0.63; r = 0.73; P < 0.01). But there was a negative correlation with obestatin of hypothalamus (r = -0.74, P < 0.01). After six weeks of STZ injection, gastric emptying (78.97% +/- 8.13% vs 44.06% +/- 5.06%) increased significantly in DM and INS groups as compared to those in NC group (35.06% +/- 3.91%, P < 0.01). Gastric emptying was positively correlated with ghrelin/obestatin of hypothalamus (r = 0.40, P < 0.05). There was no detection of GPR-39 in hypothalamus.
The rapid gastric emptying may be due to the rising levels of ghrelin and GHSR in hypothalamus during early hyperglycemia. And the duration of hyperglycemia is affected by the rising ratio of ghrelin/obestatin.
探讨糖尿病大鼠胃排空与胃饥饿素、肥胖抑制素以及下丘脑胃饥饿素受体(GHSR)、G蛋白偶联受体39(GPR-39)之间的关系。
将60只Wistar大鼠随机分为三组:正常对照组(NC,n = 20)、腹腔注射链脲佐菌素(STZ)诱导的糖尿病组(DM,n = 20)和胰岛素治疗组(INS,n = 20)。STZ注射2周和6周后,通过胃内给予酚红测量胃排空,采用酶联免疫吸附测定法(ELISA)检测下丘脑胃饥饿素和肥胖抑制素水平,采用逆转录聚合酶链反应(RT-PCR)检测GHSR和GPR-39。
STZ注射2周后,与NC组相比,DM组和INS组胃排空率(%)(74±8,40±5)、胃饥饿素水平(ng/g)(52±9,51±7)和胃饥饿素/肥胖抑制素比值(3.8±1.0,2.8±1.0)显著升高[32%±7%,(39±11)ng/g,2.1±0.8,均P < 0.05]。与NC组(21.7±4.7)相比,DM组下丘脑肥胖抑制素水平(ng/g)(14.2±2.0)显著降低,而GHSR/β-肌动蛋白显著升高(1.26±0.46对0.77±0.21,P < 0.05)。胃排空与下丘脑胃饥饿素、胃饥饿素/肥胖抑制素以及GHSR/β-肌动蛋白呈正相关(r = 0.49;r = 0.63;r = 0.73;P < 0.01)。但与下丘脑肥胖抑制素呈负相关(r = -0.74,P < 0.01)。STZ注射6周后,与NC组(35.06%±3.91%)相比,DM组和INS组胃排空(78.97%±8.13%对44.06%±5.06%)显著升高(P < 0.01)。胃排空与下丘脑胃饥饿素/肥胖抑制素呈正相关(r = 0.40,P < 0.05)。下丘脑未检测到GPR-39。
早期高血糖期间下丘脑胃饥饿素和GHSR水平升高可能导致胃排空加快。高血糖持续时间受胃饥饿素/肥胖抑制素比值升高的影响。