Glucagon
Also known as: GCG, Hyperglycemic factor, Emergency glucose peptide
Overview
Glucagon is a 29-amino acid pancreatic peptide hormone secreted by alpha cells of the islets of Langerhans in response to hypoglycemia. Its primary function is to counteract insulin by stimulating hepatic glycogenolysis and gluconeogenesis, raising blood glucose levels. In modern metabolic medicine, glucagon receptors are also implicated in energy expenditure, food intake, and lipid metabolism, making glucagon receptor agonism or modulation a component of multi-agonist weight loss therapeutics. Retatrutide, for example, is a triple GLP-1/GIP/glucagon agonist where the glucagon component contributes to energy expenditure enhancement.
Mechanism of Action
Glucagon binds the glucagon receptor (GCGR), a class B GPCR, activating adenylyl cyclase (cAMP/PKA pathway) in hepatocytes to phosphorylate glycogen phosphorylase (activating glycogenolysis) and inhibit glycogen synthase. In adipocytes, cAMP-mediated PKA phosphorylates hormone-sensitive lipase, stimulating lipolysis. In the hypothalamus, glucagon receptor signaling promotes satiety and energy expenditure. In combination metabolic agonists (GLP-1/glucagon), the glucagon component counteracts GLP-1's hypoglycemic tendency and adds thermogenic/lipolytic activity.
Potential Benefits
- Emergency hypoglycemia reversal (FDA approved)
- Hepatic glycogenolysis and gluconeogenesis stimulation
- Component of multi-agonist metabolic therapies enhancing energy expenditure
- Lipolytic activity in adipose tissue
- Satiety signaling in central nervous system
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Emergency hypoglycemia: 1 mg IM or SC (adults), 0.5 mg for children <25 kg. Nasal powder formulation: 3 mg intranasal (Baqsimi). Research metabolic dosing varies by multi-agonist compound.
Amino Acid Sequence
His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-OH
Side Effects & Safety
- Nausea and vomiting
- Hyperglycemia if excessive dosing
- Hypokalemia at high doses
Synergistic Compounds
The following compounds have been studied alongside Glucagon for potential complementary or synergistic effects:
Learn More
References & Further Reading
- [object Object]
- [object Object]