Glucagon Family Related Drug Discovery Products

Being products of the same proglucagon precursor, glucagon and glucagon-like peptides control energy homeostasis by interacting with a variety of G protein-coupled receptors. Glucagon, GLP-1, and GLP-2 are three peptides generated from proglucagon that are crucial for energy intake, absorption, and excretion. Treatment for type 2 diabetes may benefit from reducing glucagon action. GLP-1, which is released by gut endocrine cells, regulates glucose homeostasis by enhancing cell activity in response to glucose and decreasing glucagon secretion and stomach emptying. The treatment of GLP-1 is also linked to decreased food consumption, weight loss, and β−cell mass expansion via promoting β−cell proliferation and preventing apoptosis.

To meet the needs of glucagon family drug discovery, Creative Biolabs can provide a wide variety of related assays and products for our clients:

Glucagon GPCR Assays GPCR Assay Kits GPCR Cell Lines GPCR Membranes Membrane Protein Tools

Overview of Glucagon Family

The receptors for glucagon, GLP-1, and GLP-2 are members of the glucagon-secretin G protein-coupled receptor superfamily, which also consists of receptors for secretin, glucose-dependent insulinotropic polypeptide (GIP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and growth hormone-releasing hormone (GHRH). The majority of the agonists for this family of receptors are naturally occurring peptide hormones. This receptor family shares a number of structural characteristics, such as an extracellular N-terminal domain that is relatively long, highly conserved cysteine residues that most likely form disulfide bridges in the extracellular domains, an amino acid signal peptide that directs membrane localization, and a number of N-linked glycosylation sites.

Fig.1 Proteolytic Cleavage of the Proglucagon Hormone. (Estall, 2006)

• GIPR

The GIPR is a GPCR that belongs to the heterotrimeric, 7-transmembrane-spanning GPCR superfamily. The trachea, spleen, thymus, thyroid, adipose tissue, stomach, small intestine, heart, bone, lung, kidney, testis, adrenal cortex, pituitary, endothelial cells, and other regions of the central nervous system all have high levels of GIPR expression. In humans, the pancreatic β-cells seem to express the highest levels of the GIPR, which is in line with GIP's primary role as an incretin hormone.

• GLP1R

The N-terminal domain and transmembrane domains of the GLP1R have been shown to have a number of distinctive amino acid residues that are crucial for ligand binding, while the intracellular domains contain a further number of amino acid residues that are crucial for signal transduction. A number of intracellular second messengers, including Ca²⁺, cAMP, and phospholipase C, are coupled to the GLP1R via special domains that link it to Gα_s, Gα_q, Gα_i, and Gα_o.

Glucagon Family Drug Discovery

Reducing or blocking glucagon receptor signaling is a promising strategy for the treatment of type 2 diabetes, as evidenced by the therapeutic efficacy of glucagon receptor antagonists to diminish glucagon action in preclinical investigations. Moreover, a number of GLP1R agonists have shown to be highly effective in diabetic participants' clinical studies, while DPP-IV inhibitors are currently being tested in late-stage clinical trials for the treatment of type 2 diabetes. Also, in pre-clinical models of intestinal illness, GLP-2 analogues show promise.

Reference

1. Estall, J.L., & Drucker, D.J. Glucagon and glucagon-like peptide receptors as drug targets. Current pharmaceutical design. 2006, 12(14): 1731-1750.