Glucagon

Class Pancreatic hormone analog
Chemistry

Peptide hormone (29 amino acids)

Routes of administration

IV, subcutaneous, IM

Absorption

Essenially zero oral bioavailability. Absorbed well from subcutaneous depot, with onset of effect within about 20 minutes

Solubility

pKa of around 7.1; poor water solubility at high concentrations (because it self-associates into a trimer)

Distribution

VOD=0.25 L/kg; minimally protein bound

Metabolism

30% metabolised in the liver, 30% metabolised in the kidney, the rest degraded by (probably) the reticuloendothelial system

Elimination

Minimal free drug is eliminated in the urine

Time course of action

Half life is about 20-30 minutes

Target receptor

Glucagon receptors - G-protein (Gs and Gq) coupled receptors which activate adenylyl cyclase and therefore produce increased cAMP.
Mainly found in the liver

Mechanism of action

By increasing intracellular cAMP, glycogen stimulates cAMP-dependent protein kinases and therefore activates pathways of glycogen breakdown and glucose release (among many metabolic pathways)

Clinical effects

Mainly hepatic effects: Increased glycogenolysis, decreased glycogen synthesis, increased gluconeogenesis, decreased synthesis of VLDLs and increased β-oxidation of fatty acids, leading to ketosis. Also decreased release of insulin, decreased appetite, increased basal energy expenditure. In high doses, increased cardiac contractility and heart rate

Literature reference

Müller et al, 2017

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs