Abstract
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.
Highlights
Diabetes is a major chronic, systemic metabolic disease that threatens human health and reduces the quality of life [1]
Glucagon-like Peptide-1 (GLP-1) is a potent incretin hormone which is composed of 30 amino acids
It plays a critical role in glucose homeostasis via glucose-dependent insulin production and secretion, restoration of impaired β-cell secretory function and inhibition of glucagon secretion, etc
Summary
OPEN ACCESS Citation: Xu F, Wang KY, Wang N, Li G, Liu D (2017) Bioactivity of a modified human Glucagonlike peptide-1. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis, and represents a promising candidate to use for the treatment of diabetes. A chemically-synthesized, modified analogue of human GLP-1 (mGLP-1) was designed. 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
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