What is glucagon?

Glucagon is a peptide hormone of 29 amino acids produced by the alpha cells of the pancreas. Its primary role is to regulate blood sugar levels in the body.

Unlike insulin, which lowers blood sugar levels, glucagon acts to raise them when they become too low. It does this by signaling the liver to convert stored glycogen into glucose, releasing it into the bloodstream to provide energy for the body’s cells.

Glucagon is a crucial player in maintaining glucose homeostasis, ensuring that the body has a steady supply of energy. This glucagon hormone also has emerging therapeutic potential in the treatment of various metabolic disorders, including diabetes and obesity.

Glucagon was first marketed in 1960 by Eli Lilly as a subcutaneous injection. It comes now in different forms and dosages for emergency treatment of severe hypoglycemia.

How does glucagon work?

The glucagon hormone plays a crucial role in regulating blood glucose levels in the body. When used as a therapeutic drug, it is primarily employed to treat severe hypoglycemia (low blood sugar) and certain medical conditions, like diabetes, where blood glucose needs to be raised quickly.

Glucagon mechanism of action (MOA)

Glucagon acts on hepatocytes (liver cells) and adipocytes (fat cells) through various mechanism of action. In the liver, it activates the enzyme glycogen phosphorylase. This enzyme breaks down glycogen, which is stored glucose, into glucose-1-phosphate. This glucose-1-phosphate is then converted into glucose-6-phosphate and eventually into free glucose, which is released into the bloodstream. Then, glucose can be taken up by cells by the action of insulin and metabolize it to produce energy.

Glucagon also promotes gluconeogenesis in the liver. This process involves the synthesis of glucose from non-carbohydrate precursors, such as amino acids, glycerol, and lactate. Glucagon stimulates the conversion of these substrates into glucose, contributing to increased blood glucose levels.

In addition to increasing glucose production, glucagon promotes ketogenesis in the liver. Ketogenesis involves the conversion of fatty acids into ketone bodies, such as acetoacetate and beta-hydroxybutyrate. These ketone bodies can be used as an alternative energy source by tissues, including the brain, when glucose levels are low.

Another action of glucagon is the inhibition of glycolysis, the breakdown of glucose into pyruvate, in the liver. This inhibition prevents further utilization of glucose for energy production in the liver and helps conserve glucose for release into the bloodstream.

Glucagon also acts on adipose (fat) tissue. It stimulates the metabolization of triglycerides into free fatty acids and glycerol. While this doesn’t directly raise blood glucose levels, it provides an alternative source of energy for tissues and helps spare glucose.

The combined effects of glycogenolysis, gluconeogenesis, and ketogenesis in the liver, as well as the release of free fatty acids from adipose tissue, lead to an increase in blood glucose levels and mobilizing energy from stored fat.

Glucagon vs Insulin

The overall action of glucagon opposes the effects of insulin, which lowers blood glucose levels by promoting glucose uptake into cells and glycogen storage. In situations where blood sugar drops too low, such as in cases of severe insulin-induced hypoglycemia, administering glucagon as a therapeutic drug can rapidly raise blood glucose levels to prevent life-threatening complications.

What are the applications of glucagon?

Glucagon indications

Glucagon was first commercialized in 1960 by Eli Lilly for severe hypoglycemia. Other injectable products were launched over the years and the devices were further improved from a product that needs reconstitution to prefilled syringes and auto injector pens that were more convenient especially in an emergency situation.

In 2019 Eli Lilly received the approval for the first non-injectable formulation. Their nasal spray has brought convenience of an emergency treatment to a new level.

In December 2020, glucagon from Amphastar Pharmaceuticals was the first generic of glucagon approved by the FDA for injection USP, 1 mg/vial packaged in an emergency kit, for the treatment of severe hypoglycemia, which may occur in patients with diabetes mellitus.

Glucagon can also be used as a diagnostic agent during radiologic examination as it slows down movement of the gastrointestinal tract and may be used to limit intestinal motility.

How is glucagon produced?

Synthezing glucagon API

Originally produced recombinantly, glucagon can also be produced synthetically via solid phase peptide synthesis. Synthetic glucagon can be commercialized as generic if the bio- and therapeutic equivalence is shown.

With more than 20 years of experience in GMP-grade peptides, we have developed and continue to optimize processes with cutting-edge technologies and sophisticated characterization methods. With this we deliver to our customers highly purified synthetic glucagon with documentation ready for authorities’ approval.

From complex to simple: Bachem as your best glucagon supplier

We offer our customer services to simplify their lives. Drawing from our extensive experience, we understand that time, regulatory assistance, and top-notch quality are pivotal to our customers’ success. 

List of impurities and related products:

DMF

H-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

Molecular Formula

C₁₅₃H₂₂₅N₄₃O₄₉S

Relative Molecular Mass

3482.80 g/mol

CAS-Number

16941-32-5

Long-term Storage

-20 ± 5°C

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