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

TY - JOUR

T1 - Loss of inverse relationship between pulsatile insulin and glucagon secretion in patients with type 2 diabetes

AU - Menge, Björn A

AU - Grüber, Lena

AU - Jørgensen, Signe M

AU - Deacon, Carolyn F

AU - Schmidt, Wolfgang E

AU - Veldhuis, Johannes D

AU - Holst, Jens Juul

AU - Meier, Juris J

PY - 2011/8

Y1 - 2011/8

N2 - 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.

AB - 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.

KW - Aged

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Fasting

KW - Female

KW - Glucagon

KW - Humans

KW - Insulin

KW - Male

KW - Middle Aged

KW - Postprandial Period

U2 - 10.2337/db11-0251

DO - 10.2337/db11-0251

M3 - Journal article

C2 - 21677283

SN - 0012-1797

VL - 60

SP - 2160

EP - 2168

JO - Diabetes

JF - Diabetes

IS - 8

ER -