Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia

TY - JOUR

T1 - Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia

AU - Gejl, Michael

AU - Lerche, Susanne

AU - Mengel, Annette

AU - Møller, Niels

AU - Bibby, Bo Martin

AU - Smidt, Kamille

AU - Brock, Birgitte

AU - Søndergaard, Hanne

AU - Bøtker, Hans Erik

AU - Gjedde, Albert

AU - Holst, Jens Juul

AU - Hansen, Søren Baarsgaard

AU - Rungby, Jørgen

PY - 2014/1/6

Y1 - 2014/1/6

N2 - Background and Aims: Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia. Materials and Methods: We included eighteen healthy men in two randomized, double-blinded, placebo-controlled crossover studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with 18fluoro-deoxyglucose (18F-FDG) as tracer. Results: In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m2 and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m2. GLP-1 did not change MGU during normoglycemia (mean (+/- SD) 0.15+/-0.04 and 0.16+/-0.03 mmol/g/min, P = 0.46) or during hypoglycemia (0.16+/-0.03 and 0.13+/-0.04 μmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r2 = 0.64 and P = 0.018, r2 = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r2 = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found. Conclusions: While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects. ClinicalTrials.gov registration numbers: NCT00418288: (hypoglycemia) and NCT00256256: (normoglycemia).

AB - Background and Aims: Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia. Materials and Methods: We included eighteen healthy men in two randomized, double-blinded, placebo-controlled crossover studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with 18fluoro-deoxyglucose (18F-FDG) as tracer. Results: In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m2 and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m2. GLP-1 did not change MGU during normoglycemia (mean (+/- SD) 0.15+/-0.04 and 0.16+/-0.03 mmol/g/min, P = 0.46) or during hypoglycemia (0.16+/-0.03 and 0.13+/-0.04 μmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r2 = 0.64 and P = 0.018, r2 = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r2 = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found. Conclusions: While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects. ClinicalTrials.gov registration numbers: NCT00418288: (hypoglycemia) and NCT00256256: (normoglycemia).

U2 - 10.1371/journal.pone.0083758

DO - 10.1371/journal.pone.0083758

M3 - Journal article

C2 - 24400077

SN - 1932-6203

VL - 9

SP - 1

EP - 10

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 1

M1 - e83758

ER -