| Title |
An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice
|
|---|---|
| Published in |
Diabetologia, December 2016
|
| DOI | 10.1007/s00125-016-4186-y |
| Pubmed ID | |
| Authors |
Annie Hasib, Ming T. Ng, Victor A. Gault, Dawood Khan, Vadivel Parthsarathy, Peter R. Flatt, Nigel Irwin |
| Abstract |
Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla(2))GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla(2))GIP and xenin-8-Gln. Following confirmation of enzymatic stability, insulin secretory activity of (DAla(2))GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells. Acute and persistent glucose-lowering and insulin-releasing effects were then examined in vivo. Finally, the metabolic benefits of twice daily injection of (DAla(2))GIP/xenin-8-Gln was determined in high-fat-fed mice. All peptides significantly (p < 0.05 to p < 0.001) enhanced in vitro insulin secretion from pancreatic clonal BRIN-BD11 cells, with xenin (and particularly GIP)-related signalling pathways, being important for this action. Administration of (DAla(2))GIP or (DAla(2))GIP/xenin-8-Gln in combination with glucose significantly (p < 0.05) lowered blood glucose and increased plasma insulin in mice, with a protracted response of up to 4 h. All treatments elicited appetite-suppressive effects (p < 0.05), particularly (DAla(2))GIP/xenin-8-Gln and xenin-8-Gln at elevated doses of 250 nmol/kg. Twice-daily administration of (DAla(2))GIP/xenin-8-Gln or (DAla(2))GIP for 21 days to high-fat-fed mice returned circulating blood glucose to lean control levels. In addition, (DAla(2))GIP/xenin-8-Gln treatment significantly (p < 0.05) reduced glycaemic levels during a 24 h glucose profile assessment. Neither of the treatment regimens had an effect on body weight, energy intake or circulating insulin concentrations. However, insulin sensitivity was significantly (p < 0.001) improved by both treatments. Interestingly, GIP-mediated glucose-lowering (p < 0.05) and insulin-releasing (p < 0.05 to p < 0.01) effects were substantially improved by (DAla(2))GIP and (DAla(2))GIP/xenin-8-Gln treatment. Pancreatic islet and beta cell area (p < 0.001), as well as pancreatic insulin content (p < 0.05), were augmented in (DAla(2))GIP/xenin-8-Gln-treated mice, related to enhanced proliferation and decreased apoptosis of beta cells, whereas (DAla(2))GIP evoked increases (p < 0.05 to p < 0.01) in islet number. These studies highlight the clear potential of GIP/xenin hybrids for the treatment of type 2 diabetes. |
X Demographics
The data shown below were collected from the profiles of 16 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 5 | 31% |
| United Kingdom | 2 | 13% |
| Canada | 1 | 6% |
| Germany | 1 | 6% |
| Venezuela, Bolivarian Republic of | 1 | 6% |
| Denmark | 1 | 6% |
| United Arab Emirates | 1 | 6% |
| Unknown | 4 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 12 | 75% |
| Practitioners (doctors, other healthcare professionals) | 3 | 19% |
| Scientists | 1 | 6% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 19% |
| Researcher | 4 | 13% |
| Student > Master | 4 | 13% |
| Student > Bachelor | 3 | 10% |
| Lecturer | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 11 | 35% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 23% |
| Biochemistry, Genetics and Molecular Biology | 5 | 16% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
| Sports and Recreations | 2 | 6% |
| Computer Science | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 11 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 February 2017.
All research outputs
#3,775,507
of 25,732,188 outputs
Outputs from Diabetologia
#1,707
of 5,376 outputs
Outputs of similar age
#70,254
of 424,805 outputs
Outputs of similar age from Diabetologia
#42
of 65 outputs
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