The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

Kristian Karstoft; Stefan P. Mortensen; Sine H. Knudsen; Thomas Solomon

doi:10.1152/ajpendo.00520.2014

The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

Kristian Karstoft, Stefan P. Mortensen, Sine H. Knudsen, Thomas Solomon

10 Citationer (Scopus)

Abstract

The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg^_1·min^_1), and 3) glucosedependent insulinotropic polypeptide (GIP, 1.5 pmol·kg^_1·min^_1). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P ˂ 0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P ˂ 0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.

Originalsprog	Engelsk
Tidsskrift	American Journal of Physiology: Endocrinology and Metabolism
Vol/bind	308
Udgave nummer	5
Sider (fra-til)	E426–E433
Antal sider	8
ISSN	0193-1849
DOI	https://doi.org/10.1152/ajpendo.00520.2014
Status	Udgivet - 1 mar. 2015

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10.1152/ajpendo.00520.2014

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title = "The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics",

abstract = "The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg_1·min_1), and 3) glucosedependent insulinotropic polypeptide (GIP, 1.5 pmol·kg_1·min_1). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P ˂ 0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P ˂ 0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.",

author = "Kristian Karstoft and {P. Mortensen}, Stefan and {H. Knudsen}, Sine and Thomas Solomon",

note = "Copyright {\textcopyright} 2015, American Journal of Physiology - Endocrinology and Metabolism.",

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doi = "10.1152/ajpendo.00520.2014",

language = "English",

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T1 - The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

AU - Karstoft, Kristian

AU - P. Mortensen, Stefan

AU - H. Knudsen, Sine

AU - Solomon, Thomas

PY - 2015/3/1

Y1 - 2015/3/1

N2 - The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg_1·min_1), and 3) glucosedependent insulinotropic polypeptide (GIP, 1.5 pmol·kg_1·min_1). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P ˂ 0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P ˂ 0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.

AB - The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men (n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg_1·min_1), and 3) glucosedependent insulinotropic polypeptide (GIP, 1.5 pmol·kg_1·min_1). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP (P ˂ 0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P ˂ 0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.

U2 - 10.1152/ajpendo.00520.2014

DO - 10.1152/ajpendo.00520.2014

M3 - Journal article

C2 - 25564476

SN - 0193-1849

VL - 308

SP - E426–E433

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

IS - 5

ER -

The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

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