Bioactivity of a modified human Glucagon-like peptide-1.
Diabetes has become the third largest cause of death in humans worldwide. Therefore, effective treatment for this disease remains a critical issue. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis, and therefore represents a promising candidate to use for the treatment of diabetes. Native GLP-1, however, is quickly degraded in in the circulatory system; which limits its clinical application. In the present study, a chemically-synthesized, modified analogue of human GLP-1 (mGLP-1) was designed. Our analyses indicated that, relative to native GLP-1, mGLP-1 is more resistant to trypsin and pancreatin degradation. mGLP-1 promotes mouse pancreatic β-cell proliferation by up-regulating the expression level of cyclin E, CDK2, Bcl-2 and down-regulating Bax, p21, and stimulates insulin secretion. An oral glucose tolerance test indicated that mGLP-1 significantly improved glucose tolerance in mice. Intraperitoneal injections of mGLP-1 into streptozotocin (STZ)-induced type 2 diabetic mice significantly reduced blood sugar levels and stimulated insulin secretion. Oral gavages of mGLP-1 in diabetic mice did not result in significant hypoglycemic activity.
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
Fangfang
F
Xu
Department of Natural Sciences, Northeastern State University, Broken Arrow, Oklahoma, United States of America.
Kevin Yueju
KY
Wang
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
Nan
N
Wang
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
Gangqiang
G
Li
Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China.
Dehu
D
Liu
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D052216:Glucagon-Like Peptide 1