High evidence 0Moderate evidence 1Low evidence 7Very low evidence 2
Glucagon (native; Physiology) is shown as a marketed evidence record where applicable. Findings describe observed research and regulatory records; they do not provide treatment advice.
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Acute glucagon infusion raises renal plasma flow, GFR and natriuresis at the isolated GCGR level, whereas pure GLP-1R agonism is natriuretic but does not change...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingAcute glucagon infusion raises renal plasma flow, GFR and natriuresis at the isolated GCGR level, whereas pure GLP-1R agonism is natriuretic but does not change GFR/RPF at healthy baseline; the co-agonist-minus-GLP-1 logic therefore attributes any GFR/RPF rise on a co-agonist toward the GCGR arm, with both arms independently natriuretic suggesting additive natriuresis.
PopulationReview-tier (glucagon side, Farah 1983); GLP-1 contrast poles are human-primary (Skov JCEM 2013 PMID 23463656; Asmar AJP-Endo 2015 PMID 25670826) cited as contrast only.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Starvation (fasting) natriuresis has been linked to raised circulating glucagon, the likely mechanism being that glucagon increases renal excretion of organic acids by...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingStarvation (fasting) natriuresis has been linked to raised circulating glucagon, the likely mechanism being that glucagon increases renal excretion of organic acids by inhibiting their tubular reabsorption.
PopulationReview-tier synthesis; the fasting-natriuresis/glucagon link is correlational.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
Glucagon increased RNA concentration in glomerular tissue (a cAMP-independent effect), related to glomerular enlargement and basement-membrane thickening seen in...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingGlucagon increased RNA concentration in glomerular tissue (a cAMP-independent effect), related to glomerular enlargement and basement-membrane thickening seen in poorly controlled insulin-dependent diabetes (low insulin, high glucagon); the increased glomerular filtration of poorly controlled diabetes has been linked to the same hyperglucagonaemia.
PopulationReview-tier synthesis; chronic-hyperglucagonaemia/diabetes association data.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Glucagon (native; Physiology)MARKETED
renalIncrease
Low evidence
In 24 healthy young men, a 7-day high-protein versus normal-protein diet raised glomerular filtration rate by ~13% and filtration fraction, with concurrent rises in...
SourceFrank H et al., Am J Clin Nutr 2009;90(6):1509-16Source
Full findingIn 24 healthy young men, a 7-day high-protein versus normal-protein diet raised glomerular filtration rate by ~13% and filtration fraction, with concurrent rises in plasma GLUCAGON, natriuresis, urinary albumin and urea; renal plasma flow and renal vascular resistance were unchanged.
Population24 healthy young men; 7-day high-protein (2.4 g/kg/d) vs normal-protein (1.2 g/kg/d) crossover.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
At relatively large doses glucagon increased renal plasma flow, glomerular filtration and electrolyte excretion; intra-renal-arterial injection raised electrolyte...
SourceFarah AE, Pharmacol Rev 1983;35(3):181-217 (Glucagon and the circulation)Source
Full findingAt relatively large doses glucagon increased renal plasma flow, glomerular filtration and electrolyte excretion; intra-renal-arterial injection raised electrolyte excretion on the injected side with minimal/no GFR change, indicating a DIRECT renal tubular natriuretic action probably mediated via tubular cAMP and prostaglandin formation in the ascending limb and collecting ducts.
PopulationReview-tier synthesis of glucagon renal physiology (mixed-species mechanism; gross RPF/GFR/excretion rise the human-relevant datum).
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limits1983 review; primaries uncited at this locator; species-mixed (dog/rat micropuncture for the direct-tubular mechanism); 'large doses' qualifier limits transport to therapeutic exposures
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyIncrease
Low evidence
An intravenous glucagon bolus (2 or 5 mg) in 29 patients produced immediate positive inotropy, raised cardiac output and positive chronotropy, peaking within ~10 min...
SourceMurtagh JG et al., Br Heart J 1970;32(3):307Source
Full findingAn intravenous glucagon bolus (2 or 5 mg) in 29 patients produced immediate positive inotropy, raised cardiac output and positive chronotropy, peaking within ~10 min and dissipating within ~30 min; in acute myocardial infarction glucagon raised cardiac output by 42%. The classic human positive-chronotropy/inotropy dataset.
Population29 patients, single intravenous glucagon bolus 2-5 mg
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~29); short duration
Comparatorsn/a
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyNo change
Low evidence
In isolated failing and non-failing human heart tissue (atria, ventricles, sinoatrial nodes), glucagon exerted NO inotropic or chronotropic effect (with or without the...
SourceAranda-Domene R et al. (Hernandez-Cascales), Cardiovasc Diabetol 2023;22(1):128Source
Full findingIn isolated failing and non-failing human heart tissue (atria, ventricles, sinoatrial nodes), glucagon exerted NO inotropic or chronotropic effect (with or without the PDE inhibitor IBMX) and glucagon receptors were NOT detected in the human samples; a non-human positive control confirmed assay validity. The key human-primary contested-null pole.
Populationisolated failing and non-failing human heart tissue (RA/LA/RV/LV/sinoatrial node); positive control confirmed assay validity
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Glucagon's positive inotropic/chronotropic cardiac effect is mediated by adenylyl-cyclase activation and inhibition of low-Km cAMP phosphodiesterase, raising cAMP and...
SourceMery PF et al., Nature 1990;345(6271):158-61Source
Full findingGlucagon's positive inotropic/chronotropic cardiac effect is mediated by adenylyl-cyclase activation and inhibition of low-Km cAMP phosphodiesterase, raising cAMP and enhancing the cardiac L-type Ca2+ current (ICa); the effect resembles a beta-adrenergic agent but is NOT blocked by propranolol.
Populationfrog and rat ventricular myocytes
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Comparatorspropranolol
Glucagon (native; Physiology)MARKETED
heart-rate-chronotropyIncrease
Very low evidence
In isolated adult-mouse cardiac preparations, glucagon (0.1-100 nM) exerted concentration-dependent POSITIVE CHRONOTROPY in spontaneously beating right atria -...
SourceNeumann J et al., Int J Mol Sci 2025;27(1):126 (e-pub 2025-12-22)Source
Full findingIn isolated adult-mouse cardiac preparations, glucagon (0.1-100 nM) exerted concentration-dependent POSITIVE CHRONOTROPY in spontaneously beating right atria - reversed by GCGR antagonists and attenuated by the HCN-blocker ivabradine, but not by propranolol or the PDE4 inhibitor rolipram - while DECREASING force of contraction; GCGR mRNA was highest in right atrium.
Populationisolated adult-mouse cardiac preparations (spontaneously beating right atria; ventricle)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.
Glucagon (native; Physiology)MARKETED
Insulin and beta-cell functionIncrease
Moderate evidence
Glucagon acting on GCGR drives hepatic glycogenolysis and gluconeogenesis, raising plasma glucose; protein-induced hyperglucagonaemia (~8x basal) raised endogenous...
SourceAng T et al., Diabetes 2019;68(5):939-946; per corpus L2-016/L2-017Source
Full findingGlucagon acting on GCGR drives hepatic glycogenolysis and gluconeogenesis, raising plasma glucose; protein-induced hyperglucagonaemia (~8x basal) raised endogenous glucose production ~25% and rendered the liver unresponsive to insulin-mediated EGP suppression (stable-isotope tracer). The liver-alpha-cell axis: GCGR agonism increases hepatic amino-acid uptake/ureagenesis, while GCGR blockade/loss-of-function causes alpha-cell hyperplasia and hyperglucagonaemia.
Fundingacademic-Diabetes Australia Research Program
Scope limitsReused from corpus T3-011/L2-016/L2-017. Glucose-RAISING side of the offset: insulin counterbalances glucagon-on-EGP. +25% is a NET of protein bolus + gluconeogenic substrate + ~6x insulin rise (acute/supraphysiological), not a clean signal-only isolation.