Cooperberg BA, Cryer PE
Beta-Cell-Mediated Signaling Predominates Over Direct Alpha-Cell Signaling in the Regulation of Glucagon Secretion in Humans. [JOURNAL ARTICLE]
Diabetes Care 2009 Sep 3.
Objective - 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. 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 beta-cell deficient, patients with type 1 diabetes and 20 nondiabetic, demonstrably beta-cell sufficient, individuals, the latter infused with glucose to prevent hypoglycemia following glimepiride. Results - Following 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). Following 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 pm/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. Conclusions - 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.
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