Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man

TY - JOUR

T1 - Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man

AU - Hvidberg, A

AU - Nielsen, M T

AU - Hilsted, J

AU - Orskov, C

AU - Holst, J J

PY - 1994/1

Y1 - 1994/1

N2 - The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes.

AB - The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes.

KW - Adult

KW - Blood Glucose/analysis

KW - Glucagon/blood

KW - Glucagon-Like Peptide 1

KW - Glucose/metabolism

KW - Humans

KW - Insulin/blood

KW - Liver/metabolism

KW - Male

KW - Peptide Fragments/blood

KW - Protein Precursors/blood

KW - Radioimmunoassay

M3 - Journal article

C2 - 8289665

SN - 0026-0495

VL - 43

SP - 104

EP - 108

JO - Metabolism

JF - Metabolism

IS - 1

ER -