Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Boschmann, Michael; Engeli, Stefan; Dobberstein, Kerstin; Budziarek, Petra; Strauss, Anke; Boehnke, Jana; Sweep, Fred C.G.J.; Luft, Friedrich C.; He, Yan-Ling; Foley, James E.; Jordan, Jens

doi:10.1210/jc.2008-1400

Cited by 108 publications

(64 citation statements)

References 32 publications

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“…In an interesting paper, Boschmann et al . have demonstrated that vildagliptin increased post-prandial lipid mobilization and oxidation, in T2DM patients, effects mainly attributable to the activation of the adrenergic system, rather than to a peculiar metabolic action [30]. In a similar mouse model, vildagliptin administration was able not only to ameliorate the insulin resistance condition, but also to determine cardioprotection.…”

Section: Potential Positive Indirect Effects On Cardiovascular Functionmentioning

confidence: 99%

Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection

Avogaro¹,

Kreutzenberg²,

Fadini

2014

CPD

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Dipeptidyl peptidases 4 (DPP4) inhibitors are a new class of oral anti-hyperglycemic drugs for the treatment of type 2 diabetes (T2DM). They are also called “incretins” because they act by inhibiting the degradation of endogenous incretin hormones, in particular GLP-1, that mediates their main metabolic effects. DPP4 is an ubiquitous protease that regulates not only glucose and lipid metabolism, but also exhibits several systemic effects at different site levels. DPP4 inhibition improves endothelial function, reduces the pro-oxidative and the pro-inflammatory state, and exerts renal effects. These actions are mediated by different DPP4 ligands, such as cytokines, growth factors, neuotransmitters etc. Clinical and experimental studies have demonstrated that DPP4 inhibitors are efficient in protecting cardiac, renal and vascular systems, through antiatherosclerotic and vasculoprotective mechanisms. For these reasons DDP4 inhibitors are thought to be “cardiovascular protective” as well as anti-diabetic drugs. Clinical trials aimed to demonstrate the efficacy of DPP4 inhibitors in reducing cardiovascular events, independent of their anti-hyperglycemic action, are ongoing. These trials will also give necessary information on their safety.

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Section: Potential Positive Indirect Effects On Cardiovascular Functionmentioning

confidence: 99%

Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection

Avogaro¹,

Kreutzenberg²,

Fadini

2014

CPD

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“…Было установлено, что вилдаглиптин ингибирует абсорбцию триглицеридов из кишечника, снижает липолиз и со-держание триглицеридов в печени, а также увеличивает уровень норэпинефрина, что также способствует расще-плению жиров (рис. 3) [32,33,34]. Ингибиторы ДПП-4 представляют собой класс препаратов, способных обе-спечить дополнительные клинические преимущества в управлении СД2 у пациентов с избыточной массой тела и ожирением.…”

Section: сахароснижающие препараты нейтральные в отношении набора маunclassified

Obesity and type 2 diabetes: can we find a compromised treatment solution?

2017

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Диагностика, контроль, лечение Diagnosis, control, treatment ахарный диабет 2 типа (СД2) является со-временной медико-социальной проблемой вследствие широкой распространенности за-болевания и высокой частоты смертности и инвалидиза-ции по причине макро-и микрососудистых осложнений диабета. Число больных СД2 продолжает увеличиваться, достигнув уже 415 млн человек во всем мире [1]. Этому в немалой степени способствует вторая глобальная эпи-демия -ожирение. По данным ВОЗ, четверть населения планеты страдает ожирением или имеет избыточную массу тела. Большинство пациентов с СД2 имеют ожи-рение и избыточную массу тела. Наличие висцерального ожирения способствует развитию и прогрессированию СД2, в также увеличивает риск сердечно-сосудистых за-болеваний. С момента диагностики ожирение требует длительного лечения. Снижение массы тела на 5-10% ассоциируется с улучшением гликемического кон-троля, а также со снижением факторов риска развития сердечно-сосудистых заболеваний -инсулинорези-стентности, артериального давления, холестерина и три-глицеридов, маркеров воспаления и эндотелиальной дисфункции [2,3,4].Несмотря на очевидную пользу снижения веса для пациентов с СД2, добиться клинически значимого сни-жения веса на долгосрочной основе довольно сложно. В исследовании Look AHEAD активное изменение образа жизни позволило достичь снижения веса на 8,6% в тече-ние первого года наблюдения, что сопровождалось более значительным снижением уровня HbA 1c , чем в группе контроля. Однако к моменту окончания исследования через 9,6 лет отмечалось ускользание эффекта [5]. Па-циентам с СД2 сложнее снизить массу тела, чем пациен-

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“…Some studies have shown that the DPP‐4 inhibitors linagliptin and vildagliptin do not pass the BBB38, 39. However, other studies have suggested that an increased plasma level of GLP‐1 or inhibition of DPP‐4, enhance transport of GLP‐1 across the BBB18, 40.…”

Section: Biology Of Incretin Hormones In Peripheral Organs and The Brainmentioning

confidence: 99%

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Groeneveld

Kappelle

Biessels

2015

J of Diabetes Invest

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Patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Incretin‐based therapies are a class of antidiabetic agents that are of interest in relation to these cerebral complications of diabetes. Two classes of incretin‐based therapies are currently available: the glucagon‐like‐peptide‐1 agonists and the dipeptidyl peptidase‐4 ‐inhibitors. Independent of their glucose‐lowering effects, incretin‐based therapies might also have direct or indirect beneficial effects on the brain. In the present review, we discuss the potential of incretin‐based therapies in relation to dementia, in particular Alzheimer's disease, and stroke in patients with type 2 diabetes. Experimental studies on Alzheimer's disease have found beneficial effects of incretin‐based therapies on cognition, synaptic plasticity and metabolism of amyloid‐β and microtubule‐associated protein tau. Preclinical studies on incretin‐based therapies in stroke have shown an improved functional outcome, a reduction of infarct volume as well as neuroprotective and neurotrophic properties. Both with regard to the treatment of Alzheimer's disease, and with regard to prevention and treatment of stroke, randomized controlled trials in patients with or without diabetes are underway. In conclusion, experimental studies show promising results of incretin‐based therapies at improving the outcome of Alzheimer's disease and stroke through glucose‐independent pleiotropic effects on the brain. If these findings would indeed be confirmed in large clinical randomized controlled trials, this would have substantial impact.

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Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Abstract: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

Cited by 108 publications

References 32 publications

Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection

Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection

Obesity and type 2 diabetes: can we find a compromised treatment solution?

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

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