Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion

Further evidence for the intraislet insulin hypothesis

Juris J. Meier, Lise L. Kjems, Johannes D Veldhuis, Pierre Lefèbvre, Peter C. Butler

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1051-1056
Number of pages6
JournalDiabetes
Volume55
Issue number4
DOIs
StatePublished - 2006

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Glucagon
Insulin
Type 2 Diabetes Mellitus
Alloxan
Miniature Swine
Entropy
Meals
Fasting
Swine
Eating
Hormones

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion : Further evidence for the intraislet insulin hypothesis. / Meier, Juris J.; Kjems, Lise L.; Veldhuis, Johannes D; Lefèbvre, Pierre; Butler, Peter C.

In: Diabetes, Vol. 55, No. 4, 2006, p. 1051-1056.

Research output: Contribution to journalArticle

Meier, Juris J. ; Kjems, Lise L. ; Veldhuis, Johannes D ; Lefèbvre, Pierre ; Butler, Peter C. / Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion : Further evidence for the intraislet insulin hypothesis. In: Diabetes. 2006 ; Vol. 55, No. 4. pp. 1051-1056.
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