Glucagon, secreted from islet α-cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of β-cell secretory products zinc and insulin on isolated rat α-cells, intact islets, and perfused pancreata. Islet glucagon secretion was markedly zinc sensitive (IC₅₀ = 2.7 μmol/l) more than insulin release (IC₅₀ = 10.7 μmol/l). Glucose, the mitochondrial substrate pyruvate, and the ATP-sensitive K⁺ channel (K_ATP channel) inhibitor tolbutamide stimulated isolated α-cell electrical activity and glucagon secretion. Zinc opened K_ATP channels and inhibited both electrical activity and pyruvate (but not arginine)-stimulated glucagon secretion in α-cells. Insulin tran-siently increased K_ATP channel activity, inhibited electrical activity and glucagon secretion in α-cells, and inhibited pancreatic glucagon output. Insulin receptor and K_ATP channel subunit transcripts were more abundant in α- than β-cells. Transcript for the glucagon-like peptide 1 (GLP-1) receptor was not detected in α-cells nor did GLP-1 stimulate α-cell glucagon release. β-Cell secretory products zinc and insulin therefore inhibit glucagon secretion most probably by direct activation of K_ATP channels, thereby masking an α-cell metabolism secretion coupling pathway similar to β-cells.