Glucagon Human, His
Description
Definition and Basic Characteristics of Glucagon Human, His
Glucagon Human, His refers to the human form of glucagon, a 29-amino acid peptide hormone synthesized by pancreatic α-cells. The "His" designation highlights the histidine residue at the N-terminal position (position 1), critical for receptor binding and activity .
Primary Structure
Human glucagon’s sequence begins with histidine (His¹), followed by glutamine (Gln²), serine (Ser³), and glycine (Gly⁴). This sequence is conserved across species, with porcine glucagon sharing 100% homology .
| Position | Amino Acid | Role |
|---|---|---|
| 1 | His | Critical for receptor binding and activation |
| 2 | Gln | Contributes to secondary structure stability |
| 9 | Asp | Involved in G-protein coupling receptor (GPCR) interaction |
Mechanism of Action
Glucagon binds to the glucagon receptor (GCGR), a GPCR expressed in the liver, pancreas, and adipose tissue. This triggers a signaling cascade:
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Receptor Activation: Binding induces a conformational change in GCGR, activating Gαs proteins .
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cAMP Production: Gαs stimulates adenylate cyclase, increasing intracellular cAMP .
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Kinase Activation: cAMP activates protein kinase A (PKA), which phosphorylates glycogen phosphorylase kinase .
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Glycogen Breakdown: Phosphorylated kinase converts glycogen phosphorylase b (inactive) to a (active), releasing glucose-1-phosphate from glycogen .
Traditional Applications
Novel Formulations
Recent advancements address challenges with traditional glucagon (e.g., needle-based delivery):
Beyond Glucose Regulation
Recent studies highlight glucagon’s multifaceted roles:
Diagnostic and Therapeutic Challenges
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Cross-Reactivity: Early assays detected proglucagon-derived peptides (e.g., oxyntomodulin), overestimating glucagon levels .
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Biomarker Potential: New ELISA methods reveal precise glucagon dynamics in T2D, linking hypersecretion to hyperglycemia .
Regulatory Status
Product Specs
Product Science Overview
Glucagon is a peptide hormone produced by the alpha cells of the pancreas. It plays a crucial role in glucose metabolism by promoting the release of glucose into the bloodstream. Recombinant human glucagon, tagged with a polyhistidine (His) tag, is a biotechnologically engineered form of this hormone, designed for research and therapeutic purposes.
Glucagon is a 29-amino acid peptide that functions primarily to raise blood glucose levels by stimulating glycogenolysis and gluconeogenesis in the liver. The recombinant form, often expressed in yeast or bacterial systems, retains the biological activity of the native hormone. The His tag, typically added to the N- or C-terminus of the protein, facilitates purification and detection through affinity chromatography techniques.
The production of recombinant human glucagon involves the insertion of the glucagon gene into an expression vector, which is then introduced into a host organism such as yeast or E. coli. The host cells express the glucagon protein, which is subsequently purified using the His tag. This tag binds to nickel or cobalt ions, allowing for efficient isolation of the protein from the host cell lysate.
Recombinant human glucagon with a His tag is widely used in biochemical and pharmacological research. It serves as a tool for studying glucagon’s role in glucose metabolism, receptor binding, and signal transduction pathways. Additionally, it is employed in the development of therapeutic agents for conditions such as hypoglycemia and diabetes.
The His tag offers several advantages in the production and purification of recombinant proteins:
- Ease of Purification: The His tag allows for straightforward purification using immobilized metal affinity chromatography (IMAC).
- Versatility: The tag can be placed at either the N- or C-terminus of the protein without significantly affecting its function.
- Detection: The His tag can be easily detected using anti-His antibodies, facilitating protein analysis and characterization.
