A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties

Biochimica Et Biophysica Acta
Vadivel ParthsarathyVictor A Gault

Abstract

Xenin-25 is a K-cell derived gut peptide with insulin-releasing activity which is rapidly degraded following release into the circulation. We hypothesized that substitution of all naturally-occurring Lys and Arg residues with Gln would lead to prolonged enzyme resistance and enhanced biological efficacy. Peptide stability was assessed using murine plasma, in vitro insulin-releasing actions evaluated in BRIN-BD11 cells and acute glucose-lowering and insulin-releasing actions examined in high fat fed mice. For sub-chronic studies, a range of metabolic parameters and pancreatic histology were assessed in high fat fed mice which had received saline vehicle or xenin-25(gln) twice-daily for 21 days. In contrast to native xenin-25, xenin-25(gln) was resistant to plasma-mediated degradation and significantly stimulated insulin secretion in BRIN-BD11 cells. Acute administration of xenin-25(gln) in high fat fed mice significantly reduced blood glucose and increased plasma insulin concentrations. Twice-daily administration of xenin-25(gln) in high fat fed mice did not affect food intake, body weight or circulating insulin concentrations but significantly decreased blood glucose from day 9 onwards. Furthermore, glucose tolerance, glucose-m...Continue Reading

References

Oct 1, 1981·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·P R Flatt, C J Bailey
Jul 23, 2003·Regulatory Peptides·Ramona A SilvestreJosé Marco
Mar 23, 2004·Molecular & Cellular Proteomics : MCP·Jesper V OlsenMatthias Mann
Feb 13, 2014·The Journal of Endocrinology·Christine M A MartinNigel Irwin

❮ Previous
Next ❯

Citations

Apr 11, 2018·Diabetes/metabolism Research and Reviews·Sarah L CraigNigel Irwin
Apr 24, 2019·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Yusuf Adnan GucluMurat Aksit
Jun 11, 2021·Domestic Animal Endocrinology·Takenori OnagaYumiko Yasui

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biomarkers for Type 2 Diabetes

Biomarkers can help understand chronic diseases and assist in risk prediction for prevention and early detection of diseases. Here is the latest research on biomarkers in type 2 diabetes, a disease in which the body is unable to produce or properly use insulin.