Chronic Glucagon-Like Peptide-1 Infusion Sustains Left Ventricular Systolic Function and Prolongs Survival in the Spontaneously Hypertensive, Heart Failure–Prone Rat

Poornima, Indu; Brown, Suzanne B.; Bhashyam, Siva; Parikh, Pratik; Bolukoglu, Hakki; Shannon, Richard P.

doi:10.1161/circheartfailure.108.766402

Cited by 160 publications

(115 citation statements)

References 48 publications

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“…Up to now, seven DPP-4 inhibitors are usable in Japan, including sitagliptin, vildagliptin, alogliptin, linagliptin, anagliptin, teneligliptin, and saxagliptin [93][94][95] . The elevated intrinsic plasma level of GLP-1 is considered to show protective outcomes on the CV system [96] . Ojima et al [97] showed that GLP-1 receptor agonist would inhibit ADMA development in the kidney of streptozotocin-induced DM rats.…”

Section: Adma and Incretin-based Drugsmentioning

confidence: 99%

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Konya

Miuchi

Satani

et al. 2015

WJEM

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Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects. Core tip: Asymmetric dimethylarginine (ADMA) is an emerging independent biomarker for prospective cardiovascular (CV) complications. In our study, the results show that the cases with a high level of ADMA could have diabetes mellitus CV (DMCV) complications in the future within five years. Furthermore, not only ADMA but also urinary albumin was associated with DMCV complications in the multiple regression analyses. The clinical acceptation of this parameter will rely on the availability of therapies to immediately reduce ADMA such as incretin-based drugs, which could support the part of ADMA as an etiologic risk factor.

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Section: Adma and Incretin-based Drugsmentioning

confidence: 99%

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Konya

Miuchi

Satani

et al. 2015

WJEM

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“…Also, GLP-1 has been reported to improve left ventricular function and remodeling and prolong survival in rats with chronic heart failure (28). Specifically, GLP-1 increases myocardial insulin activity and glucose uptake (36,38,50) and activates kinases of the so-called reperfusion injury salvage kinase pathway (RISK pathway) (7,19). Of interest, GLP-1 has been described as an antiapopotic factor in different cell types, including cholangyocytes (29), neuronal cells (23,27,39), and pancreatic ␤-cells (6,12,26,45).…”

mentioning

confidence: 99%

Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes

Ravassa¹,

Zudaire²,

Carr

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Activation of apoptosis contributes to cardiomyocyte dysfunction and death in diabetic cardiomyopathy. The peptide glucagon-like peptide-1 (GLP-1), a hormone that is the basis of emerging therapy for type 2 diabetic patients, has cytoprotective actions in different cellular models. We investigated whether GLP-1 inhibits apoptosis in HL-1 cardiomyocytes stimulated with staurosporine, palmitate, and ceramide. Studies were performed in HL-1 cardiomyocytes. Apoptosis was induced by incubating HL-1 cells with staurosporine (175 nM), palmitate (135 μM), or ceramide (15 μM) for 24 h. In staurosporine-stimulated HL-1 cardiomyocytes, phosphatidylserine exposure, Bax-to-Bcl-2 ratio, Bad phosphorylation (Ser136), BNIP3 expression, mitochondrial membrane depolarization, cytochrome c release, caspase-3 activation, DNA fragmentation, and mammalian target of rapamycin (mTOR)/p70S6K phosphorylation (Ser2448 and Thr389, respectively) were assessed. Apoptotic hallmarks were also measured in the absence or presence of low (5 mM) and high (10 mM) concentrations of glucose. In addition, phosphatidylserine exposure and DNA fragmentation were analyzed in palmitate- and ceramide-stimulated cells. Staurosporine increased apoptosis in HL-1 cardiomyocytes. GLP-1 (100 nM) partially inhibited staurosporine-induced mitochondrial membrane depolarization and completely blocked the rest of the staurosporine-induced apoptotic changes. This cytoprotective effect was mainly mediated by phosphatidylinositol 3-kinase (PI3K) and partially dependent on ERK1/2. Increasing concentrations of glucose did not influence GLP-1-induced protection against staurosporine. Furthermore, GLP-1 inhibited palmitate- and ceramide-induced phosphatidylserine exposure and DNA fragmentation. Incretin GLP-1 protects HL-1 cardiomyocytes against activation of apoptosis. This cytoprotective ability is mediated mainly by the PI3K pathway and partially by the ERK1/2 pathway and seems to be glucose independent. It is proposed that therapies based on GLP-1 may contribute to prevent cardiomyocyte apoptosis.

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“…61 A 3-month course of continuous GLP-1 agonist infusion in spontaneously hypertensive heart failure-prone obese rats was associated with prolonged survival, preserved LV function, enhanced myocardial glucose uptake, and reduced apoptosis. 62 GLP-1 infusion in dogs with pacing-induced cardiomyopathy resulted in significant increases in stroke volume and cardiac output. 63 …”

Section: Animal Modelsmentioning

confidence: 95%