Cysteine promotes islet α-cell glucagon secretion by limiting oxidative inhibition of voltage-gated sodium channels.

Short-term cysteine depletion in human and mouse islets markedly suppresses hypoglycemia-stimulated glucagon secretion, linked to reduced α-cell Ca2+ influx and voltage-gated sodium channel activity.

• Why it matters: Diabetes changes plasma cysteine and glucagon, but how cysteine regulates α-cell glucagon release is unclear, limiting understanding of redox control of electrical excitability.
• What they did: The study depleted cysteine in isolated human and mouse islets, measured hypoglycemia-stimulated α-cell Ca2+ influx, glucagon secretion, and α-cell voltage-gated sodium channel conductance and action potential amplitude, then tested whether reducing agents could rescue NaV currents and glucose control of Ca2+ handling.
• The result: Cysteine restoration rapidly normalized glucagon secretion and α-cell Ca2+ influx, while reducing agents restored NaV currents and glucose regulation of Ca2+ handling even without cysteine, identifying reductive amplification of NaV channels as required for hypoglycemia-stimulated glucagon secretion.

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