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Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.

Forst T, Weber MM, Pfützner A - Exp Diabetes Res (2012)

Bottom Line: Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality.Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies.The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Research and Development, 55116 Mainz, Germany. thomasf@ikfe.de

ABSTRACT
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

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Related in: MedlinePlus

Schematic illustration of intracellular insulin signalling (aPKC: atypical Protein-Kinase C, eNOS: endothelial Nitric Oxide Synthase, ET1: Endothelin 1, FOX01: Forkhead Box01, IRS: Insulin Receptor Substrate, MAPK: Mitogen Activated Proteinkinase, MEK: Mitogen Activated Proteinkinase Kinase, NO: Nitric Oxide, PDK: Phosphoinositide-Dependent Kinase, PI3K: Phosphatidylinostol 3 Kinase, RAS, RAF: Proto-Oncogenes, SHC: Adapter Protein; adapted to [6]).
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Related In: Results  -  Collection


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fig2: Schematic illustration of intracellular insulin signalling (aPKC: atypical Protein-Kinase C, eNOS: endothelial Nitric Oxide Synthase, ET1: Endothelin 1, FOX01: Forkhead Box01, IRS: Insulin Receptor Substrate, MAPK: Mitogen Activated Proteinkinase, MEK: Mitogen Activated Proteinkinase Kinase, NO: Nitric Oxide, PDK: Phosphoinositide-Dependent Kinase, PI3K: Phosphatidylinostol 3 Kinase, RAS, RAF: Proto-Oncogenes, SHC: Adapter Protein; adapted to [6]).

Mentions: Beside the well-known metabolic effects of insulin, the hormone exerts important vascular effects through the activation of opposing intracellular signaling pathways. Under normal conditions, insulin provides vasodilatation and vasoprotective effects through the activation of the Phosphoinositol-3-Kinase pathway (PI-3 K) and promoting the release of NO. In contrast, in case of insulin resistance and an unphysiological release of insulin and proinsulin from the beta cells, the signal shifts from the vasoprotective PI-3 K pathway to the mitogen activated proteinkinase (MAPK) pathway (Figure 2). In this case, the vasodilating and beneficial effects of insulin turn over into the vasoconstrictive and mitogenic properties of insulin [6, 39].


Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.

Forst T, Weber MM, Pfützner A - Exp Diabetes Res (2012)

Schematic illustration of intracellular insulin signalling (aPKC: atypical Protein-Kinase C, eNOS: endothelial Nitric Oxide Synthase, ET1: Endothelin 1, FOX01: Forkhead Box01, IRS: Insulin Receptor Substrate, MAPK: Mitogen Activated Proteinkinase, MEK: Mitogen Activated Proteinkinase Kinase, NO: Nitric Oxide, PDK: Phosphoinositide-Dependent Kinase, PI3K: Phosphatidylinostol 3 Kinase, RAS, RAF: Proto-Oncogenes, SHC: Adapter Protein; adapted to [6]).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3345223&req=5

fig2: Schematic illustration of intracellular insulin signalling (aPKC: atypical Protein-Kinase C, eNOS: endothelial Nitric Oxide Synthase, ET1: Endothelin 1, FOX01: Forkhead Box01, IRS: Insulin Receptor Substrate, MAPK: Mitogen Activated Proteinkinase, MEK: Mitogen Activated Proteinkinase Kinase, NO: Nitric Oxide, PDK: Phosphoinositide-Dependent Kinase, PI3K: Phosphatidylinostol 3 Kinase, RAS, RAF: Proto-Oncogenes, SHC: Adapter Protein; adapted to [6]).
Mentions: Beside the well-known metabolic effects of insulin, the hormone exerts important vascular effects through the activation of opposing intracellular signaling pathways. Under normal conditions, insulin provides vasodilatation and vasoprotective effects through the activation of the Phosphoinositol-3-Kinase pathway (PI-3 K) and promoting the release of NO. In contrast, in case of insulin resistance and an unphysiological release of insulin and proinsulin from the beta cells, the signal shifts from the vasoprotective PI-3 K pathway to the mitogen activated proteinkinase (MAPK) pathway (Figure 2). In this case, the vasodilating and beneficial effects of insulin turn over into the vasoconstrictive and mitogenic properties of insulin [6, 39].

Bottom Line: Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality.Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies.The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Institute for Clinical Research and Development, 55116 Mainz, Germany. thomasf@ikfe.de

ABSTRACT
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

Show MeSH
Related in: MedlinePlus