Glucagon (1-29) Human

The peptide sequence HSQGTFTSDYSKYLDSRRAQDFVQWLMNT corresponds to human glucagon, a 29-amino-acid peptide hormone produced by the alpha cells of the pancreas. This hormone plays a crucial role in glucose metabolism by increasing blood glucose levels, primarily through the promotion of gluconeogenesis and glycogenolysis in the liver.

Biological Function

• Origin: Glucagon is derived from the proglucagon gene (GCG) and is secreted by pancreatic α-cells in response to hypoglycemia.

• Mechanism of Action: Upon secretion, glucagon binds to the glucagon receptor (GCGR), a G protein-coupled receptor (GPCR) predominantly expressed in the liver. This binding activates adenylate cyclase, leading to an increase in cyclic AMP (cAMP) levels, which in turn activates protein kinase A (PKA). PKA then phosphorylates target enzymes that promote gluconeogenesis and glycogenolysis, thereby increasing blood glucose levels. 

• Physiological Role: Glucagon serves as a counter-regulatory hormone to insulin, ensuring blood glucose homeostasis. While insulin lowers blood glucose levels by promoting glucose uptake and storage, glucagon increases blood glucose levels by stimulating glucose production and release.

Clinical Applications

• Therapeutic Use: Glucagon is used in the treatment of severe hypoglycemia, particularly in insulin-dependent diabetic patients. It is administered to rapidly elevate blood glucose levels when oral intake is not feasible. 

• Diagnostic Use: In diagnostic settings, glucagon is employed to assess pancreatic function and to relax the gastrointestinal tract during imaging procedures.

• Research Tool: Synthetic glucagon is used in research to study glucose metabolism, insulin secretion, and the pathophysiology of diabetes and other metabolic disorders.

Structural and Biochemical Properties

• Sequence: The amino acid sequence of human glucagon is: HSQGTFTSDYSKYLDSRRAQDFVQWLMNT

• Molecular Weight: Approximately 3,483 Daltons.

• Molecular Formula: C₁₅₃H₂₂₅N₄₃O₄₉S.

• Storage: Synthetic glucagon should be stored at -20°C to maintain stability.

Research and Development

Recent studies have focused on optimizing the glucagon sequence for medicinal purposes, aiming to improve its solubility and stability for therapeutic applications.  Additionally, glucagon receptor agonists are being explored for their potential in treating metabolic diseases beyond hypoglycemia, such as obesity and non-alcoholic fatty liver disease (NAFLD).

The peptide HSQGTFTSDYSKYLDSRRAQDFVQWLMNT represents human glucagon, a vital hormone in glucose regulation. Its clinical applications in treating hypoglycemia and its role as a research tool underscore its significance in both medical and scientific contexts.

Glucagon (1-29) Human is a synthetic research peptide in the glucagon research peptide family. Glucagon is a 29-residue peptide hormone and the endogenous ligand of the glucagon receptor, a class B G-protein-coupled receptor. Structural work with glucagon analogs supports the two-domain recognition model in which peptide contacts with the extracellular and transmembrane receptor regions cooperate in ligand binding and activation. Truncated, substituted, amidated, and labeled glucagon peptides are useful for defining receptor-contact residues and distinguishing binding from signaling.

• glucagon receptor binding assays
• cAMP signaling studies
• glucagon structure-activity analysis
• peptide/receptor interaction studies
• analytical reference applications

For fragments, substituted analogs, labeled peptides, stereochemical variants, or terminally modified forms, experimental behavior should be evaluated for the exact construct rather than assumed to match the native parent peptide. Sequence-dependent solubility, aggregation, adsorption, oxidation, and stability should be considered when establishing reconstitution, storage, and assay conditions.

1. Structure of the glucagon receptor in complex with a glucagon analogue
2. Roles of specific extracellular domains of the glucagon receptor in ligand binding and signaling