Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus

Steven P. Moberly, Kieren Mather, Zachary C. Berwick, Meredith K. Owen, Adam G. Goodwill, Eli D. Casalini, Gary Hutchins, Mark Green, Yen Ng, Robert Considine, Kevin M. Perry, Robin L. Chisholm, Johnathan Tune

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine. GLP-1 significantly augmented myocardial glucose uptake under resting conditions in lean humans, but this effect was impaired in T2DM. This observation was confirmed and extended in swine, where GLP-1 effects to augment myocardial glucose uptake during exercise were seen in lean but not in obese swine. GLP-1 did not increase myocardial oxygen consumption or blood flow in humans or in swine. Impaired myocardial responsiveness to GLP-1 in obesity was not associated with any apparent alterations in myocardial or coronary GLP1-R expression. No evidence for GLP-1-mediated activation of cAMP/PKA or AMPK signaling in lean or obese hearts was observed. GLP-1 treatment augmented p38-MAPK activity in lean, but not obese cardiac tissue. Taken together, these data provide novel evidence indicating that the cardiometabolic effects of GLP-1 are attenuated in obesity and T2DM, via mechanisms that may involve impaired p38-MAPK signaling.

Original languageEnglish
Article number365
JournalBasic Research in Cardiology
Volume108
Issue number4
DOIs
StatePublished - 2013

Fingerprint

Glucagon-Like Peptide 1
Type 2 Diabetes Mellitus
Obesity
Swine
p38 Mitogen-Activated Protein Kinases
Glucose
AMP-Activated Protein Kinases
Oxygen Consumption
Myocardial Ischemia
Insulin

Keywords

  • Cardiac
  • Diabetes
  • GLP-1
  • Glucose
  • Metabolism
  • Obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. / Moberly, Steven P.; Mather, Kieren; Berwick, Zachary C.; Owen, Meredith K.; Goodwill, Adam G.; Casalini, Eli D.; Hutchins, Gary; Green, Mark; Ng, Yen; Considine, Robert; Perry, Kevin M.; Chisholm, Robin L.; Tune, Johnathan.

In: Basic Research in Cardiology, Vol. 108, No. 4, 365, 2013.

Research output: Contribution to journalArticle

Moberly, Steven P. ; Mather, Kieren ; Berwick, Zachary C. ; Owen, Meredith K. ; Goodwill, Adam G. ; Casalini, Eli D. ; Hutchins, Gary ; Green, Mark ; Ng, Yen ; Considine, Robert ; Perry, Kevin M. ; Chisholm, Robin L. ; Tune, Johnathan. / Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. In: Basic Research in Cardiology. 2013 ; Vol. 108, No. 4.
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