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- Title
Beta-cell-mediated signaling predominates over direct alpha-cell signaling in the regulation of glucagon secretion in humans.
- Authors
Cooperberg BA; Cryer PE; Cooperberg, Benjamin A; Cryer, Philip E
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Diabetes Care, 2009, Vol 32, Issue 12, p2275
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc09-0798