TY - JOUR
T1 - Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion
T2 - Further evidence for the intraislet insulin hypothesis
AU - Meier, Juris J.
AU - Kjems, Lise L.
AU - Veldhuis, Johannes D.
AU - Lefèbvre, Pierre
AU - Butler, Peter C.
PY - 2006
Y1 - 2006
N2 - Type 2 diabetes is characterized by an ∼60% loss of β-cell mass, a marked defect in postprandial insulin secretion, and a failure to suppress postprandial glucagon concentrations. It is possible that postprandial hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin secretion. To address this, we studied eight adult Goettingen minipigs before and after an ∼60% reduction in β-cell mass induced by alloxan. Pigs were studied fasting and after ingestion of a mixed meal. Insulin and glucagon secretion were determined by deconvolution of blood hormone concentrations measured at 1-min intervals. The relationship between insulin and glucagon release was analyzed using cross-correlation and forward versus reverse cross-approximate entropy. We report that glucagon and insulin were secreted in ∼4-min pulses. Prealloxan, postprandial insulin secretion drove an ∼20% suppression of glucagon concentrations (P < 0.01), through inhibition of glucagon pulse mass. The alloxan-induced ∼60% deficit in β-cell mass lead to an ∼70% deficit in postprandial insulin secretion and loss of the postprandial insulin-driven suppression of glucagon secretion. We conclude that postprandial hyperglucagonemia in type 2 diabetes is likely due to loss of intraislet postprandial suppression of glucagon secretion by insulin.
AB - Type 2 diabetes is characterized by an ∼60% loss of β-cell mass, a marked defect in postprandial insulin secretion, and a failure to suppress postprandial glucagon concentrations. It is possible that postprandial hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin secretion. To address this, we studied eight adult Goettingen minipigs before and after an ∼60% reduction in β-cell mass induced by alloxan. Pigs were studied fasting and after ingestion of a mixed meal. Insulin and glucagon secretion were determined by deconvolution of blood hormone concentrations measured at 1-min intervals. The relationship between insulin and glucagon release was analyzed using cross-correlation and forward versus reverse cross-approximate entropy. We report that glucagon and insulin were secreted in ∼4-min pulses. Prealloxan, postprandial insulin secretion drove an ∼20% suppression of glucagon concentrations (P < 0.01), through inhibition of glucagon pulse mass. The alloxan-induced ∼60% deficit in β-cell mass lead to an ∼70% deficit in postprandial insulin secretion and loss of the postprandial insulin-driven suppression of glucagon secretion. We conclude that postprandial hyperglucagonemia in type 2 diabetes is likely due to loss of intraislet postprandial suppression of glucagon secretion by insulin.
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U2 - 10.2337/diabetes.55.04.06.db05-1449
DO - 10.2337/diabetes.55.04.06.db05-1449
M3 - Article
C2 - 16567528
AN - SCOPUS:33745301045
SN - 0012-1797
VL - 55
SP - 1051
EP - 1056
JO - Diabetes
JF - Diabetes
IS - 4
ER -