Novel enzyme‐resistant pancreatic polypeptide analogs evoke pancreatic beta‐cell rest, enhance islet cell turnover, and inhibit food intake in mice DOI Creative Commons

Wuyun Zhu,

Neil Tanday, Ryan A. Lafferty

et al.

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Pancreatic polypeptide (PP) is a postprandial hormone secreted from pancreatic islets that activates neuropeptide Y4 receptors (NPY4Rs). PP known to induce satiety but effects at the level of endocrine pancreas are less well characterized. In addition, rapid metabolism by dipeptidyl peptidase‐4 (DPP‐4) limits investigation native peptide. Therefore, in present study, five novel amino acid substituted and/or fatty derivatized analogs were synthesized, namely [P 3 ]PP, [K 13 Pal]PP, ,K [N‐Pal]PP, and [N‐Pal,P their impact on beta‐cell function, as appetite regulation glucose homeostasis investigated. All displayed increased resistance DPP‐4 degradation. all peptides inhibited alanine‐induced insulin secretion BRIN‐BD11 beta cells. Native related (10 −8 10 −6 M), especially ]PP significantly protected against cytokine‐induced apoptosis promoted cellular proliferation, with dependent NPY4R for barring ]PP. mice, peptides, except [N‐Pal]PP evoked dose‐dependent (25, 75, 200 nmol/kg) suppression appetite, further augmenting glucagon‐like peptide‐1 (GLP‐1) cholecystokinin (CCK) induced reductions food intake. The had no obvious detrimental effect tolerance they did not noticeably impair glucose‐regulatory actions GLP‐1 or CCK. conclusion, Pro substitution PP, either alone together mid‐chain acylation, creates benefits rest, islet cell turnover, energy may be applicable treatment diabetes obesity.

Language: Английский

Macromolecules from mushrooms, venoms, microorganisms, and plants for diabetes treatment - Progress or setback? DOI
Asmaa Chbel, Ayoub Lafnoune, Imane Nait Irahal

et al.

Biochimie, Journal Year: 2024, Volume and Issue: 227, P. 119 - 128

Published: July 10, 2024

Language: Английский

Citations

4
Novel enzyme‐resistant pancreatic polypeptide analogs evoke pancreatic beta‐cell rest, enhance islet cell turnover, and inhibit food intake in mice DOI Creative Commons

Wuyun Zhu,

Neil Tanday, Ryan A. Lafferty

et al.

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: April 18, 2024

Abstract Pancreatic polypeptide (PP) is a postprandial hormone secreted from pancreatic islets that activates neuropeptide Y4 receptors (NPY4Rs). PP known to induce satiety but effects at the level of endocrine pancreas are less well characterized. In addition, rapid metabolism by dipeptidyl peptidase‐4 (DPP‐4) limits investigation native peptide. Therefore, in present study, five novel amino acid substituted and/or fatty derivatized analogs were synthesized, namely [P 3 ]PP, [K 13 Pal]PP, ,K [N‐Pal]PP, and [N‐Pal,P their impact on beta‐cell function, as appetite regulation glucose homeostasis investigated. All displayed increased resistance DPP‐4 degradation. all peptides inhibited alanine‐induced insulin secretion BRIN‐BD11 beta cells. Native related (10 −8 10 −6 M), especially ]PP significantly protected against cytokine‐induced apoptosis promoted cellular proliferation, with dependent NPY4R for barring ]PP. mice, peptides, except [N‐Pal]PP evoked dose‐dependent (25, 75, 200 nmol/kg) suppression appetite, further augmenting glucagon‐like peptide‐1 (GLP‐1) cholecystokinin (CCK) induced reductions food intake. The had no obvious detrimental effect tolerance they did not noticeably impair glucose‐regulatory actions GLP‐1 or CCK. conclusion, Pro substitution PP, either alone together mid‐chain acylation, creates benefits rest, islet cell turnover, energy may be applicable treatment diabetes obesity.

Language: Английский

Citations

1