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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: C-Peptide, Diabetes Mellitus, Type 1, Eating, Epinephrine, Fasting, Fatty Acids, Nonesterified, Female, Glucagon, Glucagon-Secreting Cells, Homeostasis, Humans, Hypoglycemic Agents, Insulin-Secreting Cells, Male, Reference Values, Signal Transduction, Sulfonylurea Compounds.
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Does beta-cell-mediated signaling predominate over direct alpha-cell signaling in the regulation of glucagon secretion in humans? Context: Given evidence of both indirect and direct signaling, we tested the hypothesis that increased beta-cell-mediated signaling of alpha-cells negates direct alpha-cell signaling in the regulation of glucagon secretion in humans. 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 beta-cell-deficient patients with type 1 diabetes and 20 nondiabetic, demonstrably beta-cell-sufficient individuals; the latter were infused with glucose to prevent hypoglycemia after glimepiride. After the mixed meal, plasma glucagon concentrations increased from 22 +/- 1 pmol/l (78 +/- 4 pg/ml) to 30 +/- 2 pmol/l (103 +/- 7 pg/ml) in the patients with type 1 diabetes but were unchanged from 27 +/- 1 pmol/l (93 +/- 3 pg/ml) to 26 +/- 1 pmol/l (89 +/- 3 pg/ml) in the nondiabetic individuals (P < 0.0001). After glimepiride, plasma glucagon concentrations increased from 24 +/- 1 pmol/l (83 +/- 4 pg/ml) to 26 +/- 1 pmol/l (91 +/- 4 pg/ml) in the patients with type 1 diabetes and decreased from 28 +/- 1 pmol/l (97 +/- 5 pg/ml) to 24 +/- 1 pmol/l (82 +/- 4 pg/ml) in the nondiabetic individuals (P < 0.0001). Thus, in the presence of both beta-cell and alpha-cell secretory stimuli (increased amino acid and glucose levels, a sulfonylurea) glucagon secretion was prevented when beta-cell secretion was sufficient but not when beta-cell secretion was deficient.
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These data indicate that, among the array of signals, indirect reciprocal beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans. Final Decision: yes