中国病理生理杂志2024，Vol.40Issue(5)：890-898,9.DOI:10.3969/j.issn.1000-4718.2024.05.014
反复低血糖增加1型糖尿病小鼠肠GLP-1的表达及分泌
Recurrent hypoglycemia increases intestinal GLP-1 expression and secre-tion in type 1 diabetic mice
摘要
Abstract
AIM:To establish a model of recurrent hypoglycemia(RH)in mice with type 1 diabetes mellitus(T1DM)and to investigate the expression and effects of glucagon-like peptide-1(GLP-1)in the intestines of the model mice.METHODS:The T1DM model was established by induction with streptozotocin.Starting from the 15th day of T1DM,the mice in RH group were injected intraperitoneally with short-acting insulin,experiencing 1 episode of hyperin-sulinemic hypoglycemia every 3 days over 5 episodes,to establish the RH model in T1DM mice.Body weight,blood glu-cose,and activity status of the mice were recorded.Enzyme-linked immunosorbent assay(ELISA)was used to measure plasma adrenaline,glucagon(GCG),GLP-1,and somatostatin(SST)levels after the fifth episode of hypoglycemia for 60 min.Immunofluorescence staining was utilized to detect the expression of intestinal GLP-1 and hormone secretions from pancreatic α and δ cells in each group.Western blot was employed to detect protein expressions of GLP-1,GLP-1 receptor(GLP-1R),and prohormone convertase 1/3(PC1/3)in the intestine.RESULTS:Blood glucose and body weight met the standards for T1DM mice.During the 5 episodes of hypoglycemia,blood glucose levels in the RH group dropped to(3.3±0.5)mmol/L for more than 60 min during each episode of hypoglycemia,along with levels of plasma adrenaline and gluca-gon and the behavioral changes of RH mice during hypoglycemia,which met the modeling criteria of RH and impaired hy-poglycemic counterregulation in diabetic mice.ELISA detection showed that the plasma adrenaline and GCG levels were lower in RH group than those in T1DM group(P<0.01),while the plasma active GLP-1 and SST levels in mice were sig-nificantly higher in RH group(P<0.01).Immunofluorescence analysis showed that intestinal GLP-1 expression and pan-creatic SST secretion increased in RH group(P<0.01),while GCG secretion decreased(P<0.01).Western blot analysis showed that the levels of intestinal active GLP-1 and GLP-1R in RH group were significantly higher than those in T1DM group(P<0.01).CONCLUSION:Recurrent hypoglycemia in T1DM mice leads to increased intestinal GLP-1 expres-sion and secretion,which is closely related to the formation or aggravation of impaired hypoglycemic counterregulation.关键词
1型糖尿病/低血糖反调节障碍/胰高血糖素样肽1/肠道/胰腺Key words
type 1 diabetes mellitus/impaired hypoglycemic counterregulation/glucagon-like peptide-1/in-testine/pancreas分类
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靳方馨,赵晶晶,王岩,李敏讷,李如江,郭军堂..反复低血糖增加1型糖尿病小鼠肠GLP-1的表达及分泌[J].中国病理生理杂志,2024,40(5):890-898,9.基金项目
国家自然科学基金面上项目(No.81471048) （No.81471048）
