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OBJECTIVE Given evidence of both indirect and direct signaling, we tested the hypothesis that increased ?-cell–mediated signaling of ?-cells negates direct ?-cell signaling in the regulation of glucagon secretion in humans. RESEARCH DESIGN AND METHODS We measured plasma glucagon concentrations before and after ingestion of a formula mixed meal and, on a separate occasion, ingestion of the sulfonylurea glimepiride in 24 basal insulin-infused, demonstrably ?-cell–deficient patients with type 1 diabetes and 20 nondiabetic, demonstrably ?-cell–sufficient individuals; the latter were infused with glucose to prevent hypoglycemia after glimepiride.

Cryer, MDFrom the Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St.

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