TY - JOUR
T1 - Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes
AU - Vella, Adrian
AU - Shah, Pankaj
AU - Basu, Rita
AU - Basu, Ananda
AU - Holst, Jens J.
AU - Rizza, Robert A.
PY - 2000/4
Y1 - 2000/4
N2 - Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol · kg-1 · min-1) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal- (1.21 ± 0.15 vs. 1.32 ± 0.19 mol/l per 6 h) and prandial (0.56 ± 0.14 vs. 0.56 ± 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 ± 0.3 vs. -3.1 ± 0.2 μmol/kg) and prandial (-3.1 ± 0.4 vs. -3.0 ± 0.6 μmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.
AB - Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol · kg-1 · min-1) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal- (1.21 ± 0.15 vs. 1.32 ± 0.19 mol/l per 6 h) and prandial (0.56 ± 0.14 vs. 0.56 ± 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 ± 0.3 vs. -3.1 ± 0.2 μmol/kg) and prandial (-3.1 ± 0.4 vs. -3.0 ± 0.6 μmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.
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U2 - 10.2337/diabetes.49.4.611
DO - 10.2337/diabetes.49.4.611
M3 - Article
C2 - 10871199
AN - SCOPUS:0034111103
SN - 0012-1797
VL - 49
SP - 611
EP - 617
JO - Diabetes
JF - Diabetes
IS - 4
ER -