Aspartimide Modified Galanin Analogue Antagonizes Galanin Action on Insulin Secretion

Abstract

Aspartimide (Asi) formation is one of the most serious side reactions that can occur both during solid phase synthesis and storage of peptides containing aspartic acid. Although numerous studies on the mechanism of Asi formation conducted so far, the problem still remains unresolved and relatively little is known about the impact of this side reaction on biological properties of such modified peptides. In the present work we characterized the effect of Asi formation on biological properties of galanin(1-15) analogue modified in position 14 with aspartic acid, investigating its action on rat isolated gastric smooth muscles and glucose-induced insulin secretion from rat isolated islets of Langerhans. Our results show that this side process may adversely affect biological properties of such modified peptides. As we expected, modification of GAL(1-15)NH(2) structure changed the interaction of GAL(1-15)NH(2) with its receptors and consequently yielded peptide which, in studies on insulin secretion, showed insulinotropic- and antagonistic activities as compared to Asi-free analogue.

Elevated galanin may predict the risk of type 2 diabetes mellitus for development of Alzheimer’s disease

“…An administration of galanin inhibits basal insulin secretion in a dose-dependent manner (Manabe et al, 2003). This inhibition may be blocked by its antagonists (Olkowicz et al, 2007;Ruczyński et al, 2002Ruczyński et al, , 2010 (Tang et al, 2012). These results showed that galanin has a suppressive role in physiologic insulin secretion and that G(o)2 is a major transducer for the inhibitory regulation of insulin secretion.…”

“…There is growing evidence indicating a suppressive role of galanin in the release of insulin from the pancreatic islets (Manabe et al, 2003;Olkowicz et al, 2007;Ruczyński et al, 2002Ruczyński et al, , 2010Tang et al, 2012). An administration of galanin inhibits basal insulin secretion in a dose-dependent manner (Manabe et al, 2003).…”

Ingestive Peptides – An Emerging Tool for Diagnostics and Therapeutics: A Review

“…To date, however, few papers have summarized the effect of the galanin peptide family on metabolism of glucose and resistance of insulin as yet. Galanin strongly inhibits the secretion of insulin in dogs, pigs and rats (McDonald et al 1985;Lindskog et al 1990;Manabe et al 2003;Ruczynski et al 2010;Tang et al 2012;Fang et al 2014).…”

Crosstalk between exercise and galanin system alleviates insulin resistance

“…Numerous animal experiments indicated a suppressive effect of galanin on insulin release from the pancreatic islets in a dosedependent manner (Ruczyński et al, 2010;Tang et al, 2012). But this inhibitive effect of galanin on insulin secretion does not interfere its beneficial role to elevate insulin sensitivity of subjects (see Table 2).…”