Loss of Inverse Relationship Between Pulsatile Insulin and Glucagon Secretion in Patients With Type 2 Diabetes

  1. Juris J. Meier1
  1. 1Department of Medicine I, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany
  2. 2Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, Minnesota
  1. Corresponding author: Juris J. Meier, juris.meier{at}


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.

  • Received February 24, 2011.
  • Accepted May 8, 2011.

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  1. Diabetes vol. 60 no. 8 2160-2168
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