Insulin-like peptide 5 fails to improve metabolism or body weight in obese mice

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2019-10, Vol.120, p.170116-170116, Article 170116
• Main Authors: Zaykov, Alexander N., Gelfanov, Vasily M., Perez-Tilve, Diego, Finan, Brian, DiMarchi, Richard D.
• Format: Article
• Language: English
• Subjects: Glucose sensitivity; INSL5; Metabolism; Obesity
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2019.170116

•Daily high dose of INSL5 was administered to normal and obese mice for a week.•No meaningful effect on body weight, food intake or glucose sensitivity.•A non-conventional [1 + 2] synthetic strategy is presented.•An isomer of INSL5 with inverse disulfides (A8-B19, A21-B7) retains high potency. Insulin-like peptide 5 (INSL5) is a member of the insulin-like family of peptides. It has been reported to be orexigenic in rodent models of obesity with impaired glucose metabolism. We attempted to confirm this property as a first step in establishing the ability of INSL5 to successfully integrate with other agents more proven in their ability to reverse obesity and improve metabolism. INSL5 was chemically synthesized by two alternative methods to a native form and one that was site-specifically conjugated to a 20 KDa polyethylene glycol (PEG) polymer. The pharmacology of each peptide was assessed by high-dose chronic administration in normal and obese mice. INSL5 failed to produce pharmacologically relevant effects on food intake, body weight or glucose control indicative of a negligible role of the peptide in the control of feeding and glucose metabolism.