Recurrent hypoglycemia increases intestinal GLP-1 expression and secre-tion in type 1 diabetic mice
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.
type 1 diabetes mellitusimpaired hypoglycemic counterregulationglucagon-like peptide-1in-testinepancreas
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