The GLP receptors belong to a family comprising two members: the GLP-1 receptor (GLP1R, or GLP-1R) and the GLP-2 receptor (GLP2R, or GLP-1R), which can be activated by glucagon-like peptides (GLPs). Firstly， GLP-1 can enhance beta-cell function, insulin secretion, and suppresses glucagon release and hepatic glucose output. Secondly, it can reduce the rate of gastric emptying and acid secretion, resulting in appetite reduction and contributing to weight loss. However, GLP-1 has only one known receptor, GLP1R, which has a broad spectrum of signaling profiles. By regulating insulin secretion, carbohydrate metabolism, and appetite, GLP-1’s effects have potential clinical value in the research of type 2 diabetes and obesity. In fact, Multiple GLP-1R agonists have entered clinical trials, with some, such as semaglutide, progressing to approval.

Semaglutide is a GLP-1 Receptor Agonist and can be used for the research of Type 2 Diabetes Research

In vivo, The plasma half-life of Semaglutide (i.v.) in miniature pigs is 46 hours. And Semaglutide (s.c.) has an MRT of 63.6h. Secondly, Semaglutide improves MPTP-induced motor impairments. Meanwhile, Semaglutide rescues the decrease of tyrosine hydroxylase (TH) levels, alleviates the inflammation response, reduces lipid peroxidation, and inhibits the apoptosis pathway. In addition, Semaglutide also increases autophagy-related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum. As well as the long-acting GLP-1 analog semaglutide is superior to NN-2211 in most parameters.

In sum, Semaglutide, a long-acting GLP-1 analogue, is a GLP-1 receptor agonist. Semaglutide has the potential for type 2 diabetes research.

Reference:

[1] Zhang X, et al. Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. Cell Rep. 2021;36(2):109374.