Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes

Björn A. Menge, Lena Grüber, Signe M. Jørgensen, Carolyn F. Deacon, Wolfgang E. Schmidt, Johannes D. Veldhuis, Jens J. Holst, Juris J. Meier

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

OBJECTIVE - In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known. RESEARCH DESIGN AND METHODS - Twelve patients with type 2 diabetes and 13 nondiabetic individuals were examined in the fasting state and after mixed meal ingestion. Deconvolution analyses were performed on insulin and glucagon concentration time series sampled at 1-min intervals. RESULTS - Both insulin and glucagon were secreted in distinct pulses, occurring at ∼5-min intervals. In patients with diabetes, postprandial insulin pulse mass was reduced by 74% (P < 0.001). Glucagon concentrations were increased in the patients during fasting and after meal ingestion (P < 0.05), specifically through an increased glucagon pulse mass (P < 0.01). In healthy subjects, the increase in postprandial insulin levels was inversely related to respective glucagon levels (P < 0.05). This relationship was absent in the fasting state and in patients with diabetes. CONCLUSIONS - Glucagon and insulin are secreted in a coordinated, pulsatile manner. A plausible model is that the postprandial increase in insulin burst mass represses the corresponding glucagon pulses. Disruption of the insulin-glucagon interaction in patients with type 2 diabetes could potentially contribute to hyperglucagonemia.

Original languageEnglish (US)
Pages (from-to)2160-2168
Number of pages9
JournalDiabetes
Volume60
Issue number8
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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