GLP-1/GCG Protein, Human (HEK293, His)

GLP-1 and GCG are two proteins derived from the same precursor protein, which is encoded by the GCG-glucagon gene. The GCG protein is a counterregulatory hormone to insulin, playing a crucial role in glucose metabolism by increasing gluconeogenesis and reducing glycolysis to regulate blood glucose levels. GLP-1 protein, secreted by intestinal endocrine cells, promotes insulin secretion, regulates gastrointestinal motility, and inhibits the secretion of GCG protein. GLP-1/GCG protein, Human (HEK293, His), is a recombinant GLP-1/GCG protein expressed by HEK293 cells, with a His tag at the C-terminus, and is composed of 160 amino acids (R21-K180)^{[1][2][3][4][5][6][7][8][9][10]}.

GCG protein, also known as glucagon, is secreted by pancreatic α-cells and plays an important role in glucose metabolism and homeostasis. As a counterregulatory hormone to insulin, GCG protein counteracts the glucose-lowering effects of insulin when blood glucose levels drop, helping to maintain glucose balance in the body by raising blood sugar levels. In diabetes, GCG protein plays a key role in initiating and maintaining hyperglycemic conditions. Beyond regulating glucose metabolism, GCG protein also participates in lipid metabolism regulation^[1][2][3].
GLP-1 protein is a hormone secreted by the intestine, and it plays a significant role in regulating blood glucose levels and maintaining gastrointestinal function.
Blood Glucose Regulation: GLP-1 protein enhances the glucose sensitivity of pancreatic β-cells by binding to receptors on their surface, leading to increased insulin secretion when blood glucose levels are high. Additionally, GLP-1 protein can promote the regeneration of islet cells and the proliferation of pancreatic β-cells, while possibly inhibiting β-cell apoptosis, thereby protecting islet function^[4].
Gastrointestinal Function: GLP-1 protein helps maintain normal gastrointestinal function by inhibiting the secretion of GCG protein. It also enhances the uptake, utilization, and storage of glucose in peripheral tissues by regulating satiety. Moreover, GLP-1 protein promotes the growth of intestinal epithelium, contributing to intestinal health^[5].
In addition, GLP-1 protein can regulate the hypothalamic-pituitary axis (HPA) by influencing the secretion of LH, TSH, CRH, oxytocin, and antidiuretic hormone^[5].
Anti-inflammatory Effects: GLP-1 protein has anti-inflammatory effects on the islets and adipose tissues by reducing the production of inflammatory cytokines and the infiltration of immune cells into tissues. Furthermore, GLP-1 protein has shown anti-inflammatory effects in various chronic inflammatory diseases, including type 1 and type 2 diabetes, atherosclerosis, neurodegenerative diseases, non-alcoholic fatty liver disease, and diabetic nephropathy^[6].

The GCG protein (Human) (100 nM, 1 hour) can enhance insulin secretion by binding to the GCG protein receptor on pancreatic β-cells under the stimulation of physiological glucose concentrations (5 mM)^[7].
When pancreatic α-cells are exposed to GLP-1 protein (Human) (100 nM, 72 hours) for an extended period, the GLP-1 protein (Human) promotes the synthesis and release of GLP-1 by stimulating the transcription factor Pax6 and the protein convertase PC1/3 in pancreatic α-cells^[8].

The GCG protein (Human) (150 μg/kg, intraperitoneally, once daily for 5 days) can stimulate thermogenesis in brown adipose tissue in Sprague-Dawley rats^[9].
The GCG protein (Human) (0.3 μg/kg and 0.6 μg/kg, i.p., single dose; 0.6 μg/kg, s.c., single dose) significantly increases glucose levels in female farm pigs. Compared to subcutaneous injection, intraperitoneal administration induces a more rapid rise in blood glucose levels^[10].

Human

HEK293

C-6*His

P01275 (R21-K180)

2641  [NCBI]

RSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLAARDFINWLIQTKITDRK

Approximately 19-21 kDa

Greater than 95% as determined by reducing SDS-PAGE.

Solution.

Supplied as a 0.2 μm filtered solution of 20 mM Tris-HCl, 200 mM NaCl, 1 mM DTT, 50% Glycerol, pH 8.0.

<1 EU/μg, determined by LAL method.

Stored at -80°C for 1 year. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Müller TD, et al. The New Biology and Pharmacology of Glucagon. Physiol Rev. 2017 Apr;97(2):721-766.  [Content Brief]

  [2]. Zeigerer A, et al. Glucagon's Metabolic Action in Health and Disease. Compr Physiol. 2021 Apr 1;11(2):1759-1783.  [Content Brief]

  [3]. Jiang G, et al. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8.  [Content Brief]

  [4]. Ellingsgaard H, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011 Oct 30;17(11):1481-9.  [Content Brief]

  [5]. https://pubmed.ncbi.nlm.nih.gov/12554744/

  [6]. Lee YS, et al. Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control. Mediators Inflamm. 2016;2016:3094642.  [Content Brief]

  [7]. Zhang Y, et al. Glucagon Potentiates Insulin Secretion Via β-Cell GCGR at Physiological Concentrations of Glucose. Cells. 2021 Sep 21;10(9):2495.  [Content Brief]

  [8]. Piro S, et al. Chronic exposure to GLP-1 increases GLP-1 synthesis and release in a pancreatic alpha cell line (α-TC1): evidence of a direct effect of GLP-1 on pancreatic alpha cells. PLoS One. 2014 Feb 28;9(2):e90093.  [Content Brief]

  [9]. The GCG protein (Human) (150 μg/kg, intraperitoneally, once daily for 5 days) can stimulate thermogenesis in brown adipose tissue in Sprague-Dawley rats^[9].
   [Content Brief]

  [10]. Åm MK, et al. Intraperitoneal and subcutaneous glucagon delivery in anaesthetized pigs: effects on circulating glucagon and glucose levels. Sci Rep. 2020 Aug 13;10(1):13735.  [Content Brief]