Glucagon-like peptide–1 and candesartan additively improve glucolipotoxicity in pancreatic β-cells

Wang, Hongwei; Mizuta, Masanari; Saitoh, Yoshiko; Noma, K.; Ueno, Hiroaki; Nakazato, Masamitsu

doi:10.1016/j.metabol.2010.11.004

Cited by 38 publications

(22 citation statements)

References 53 publications

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“…Studies in animal models have yielded that GLP-1 could have a protective effect in diabetic nephropathy by reducing mesangial reactive oxygen formation and MCP-1 expression in response to advanced glycosylation products exposure (40) and by reducing albuminuria (41). In addition, GLP-1 has a beneficiary role on pancreatic beta cell physiology by reduce glucolipotoxicity induced apoptosis through activation of the PI3K pathway (42) and by up-regulating GLUT-2 expression, ultimately leading to enhanced insulin secretion (43, 44). …”

Section: Discussionmentioning

confidence: 99%

GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways

2013

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Introduction Novel anti-diabetic medications that mimic or augment the physiological actions of GLP-1 improve cardiovascular risk factors in diabetics and GLP-1 has been proposed to have a beneficial role in the cardiovascular system. GLP-1 may have a direct cardioprotective role by decreasing infarct size and protecting from ischemia-reperfusion injury while prolonging survival in rodent models. The mechanisms underlying these observations remain largely unknown. In vitro studies suggest that GLP-1 may promote endothelial cell proliferation, but no study to date has evaluated a potential direct effect of GLP-1 on angiogenesis. Specific Aim To evaluate whether GLP-1 affects angiogenesis in humans and to elucidate underlying molecular mechanisms. Material and Methods We utilized a 3D culture system where spherules of human umbilical vein endothelial cells (HUVECs) embedded in a collagen scaffold were treated with escalating doses of human recombinant GLP-1 (50-2000nM) and the formation of new vessels was observed and quantified. Signaling inhibitors were utilized to identify molecular pathways through which GLP-1 promotes angiogenesis. Results We demonstrate that GLP-1 promotes angiogenesis in a dose-dependent manner. The maximum effect on angiogenesis was observed at a GLP-1 dose of 500nM, while increased angiogenesis occurred in response to doses ranging from 200nM to 1000nM. Pre-treatment of the system with Akt inhibitor IV, Bisindolylmaleimide (PKC inhibitor) and src inhibitor I resulted in a significant decrease of the GLP-1 induced angiogenesis. Conclusions This is the first study to demonstrate that GLP-1 promotes angiogenesis in a HUVEC three dimensional in vitro model. This effect requires pharmacological doses and is mediated through the Akt, PKC and src pathways.

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Section: Discussionmentioning

confidence: 99%

GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways

2013

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“…It protects the progression of experimental autoimmune myocarditis to dilated cardiomyopathy in rats via modulation of ACE 2, Ang (1-7) and Mas receptor pathway [3]. In type 2 DM, co-treatment with glucagon like peptide-1, candesartan may promote the survival of β-cells [13]. In selecting candesartan as a therapeutic agent, we could also consider its effect on β-cells survival so that the heart failure patients with DM can benefit with this advantage of candesartan.…”

Section: Candesartanmentioning

confidence: 99%

Angiotensin receptor blockers: Focus on cardiac and renal injury

Arumugam

Sreedhar

Thandavarayan

et al. 2016

Trends in Cardiovascular Medicine

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“…Wang et al demonstrated that combination treatment of GLP-1 and the ARB candesartan exerted an additive anti-apoptotic effect in isolated mouse pancreatic islets. 21 Although the efficacy of DPP-4 inhibitors has been studied widely in humans, the prevalence of hypertension and concurrent administration of antihypertensive agents have not yet been addressed. [22][23][24][25][26] In this study, we showed for the first time that the DPP-4 inhibitor sitagliptin could exert protective effects on pancreatic β-cells in T2DM patients treated with ARBs.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibitor sitagliptin improves pancreatic β-cell function in hypertensive diabetic patients treated with angiotensin receptor blockers

Fukui

Kawahito

Wakana

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Introduction: Dipeptidyl peptidase (DPP)-4 inhibitors, a novel oral anti-diabetic agents, exert a protective effect on pancreatic β-cell function in patients with type 2 diabetic mellitus (T2DM). However, their beneficial effect in hypertensive T2DM patients treated with angiotensin receptor blockers (ARBs) has not been investigated. Methods: In this open-label multicenter randomized study, a total of 55 hypertensive T2DM patients treated with ARBs were randomly assigned to receive the DPP-4 inhibitor sitagliptin or sulfonylurea (SU). Results: After 24 weeks of treatment, a significant reduction in fasting blood glucose was only observed in the sitagliptin group, while HbA1c was significantly reduced in both groups. Homeostasis model assessment of insulin resistance was not significantly improved in either group. Indicators of pancreatic β-cell function, including proinsulin to insulin ratio and homeostasis model assessment of β-cell function, were significantly improved in the sitagliptin group, but not in the SU group. The beneficial effects of sitagliptin were observed in hypoglycemic drug naïve patients, but not in patients who had received SU monotherapy prior to the study. Conclusion: Treatment with the DPP-4 inhibitor sitagliptin might exert beneficial effects on pancreatic β-cell function in ARB-treated T2DM patients and its efficacy might be more pronounced in hypoglycemic drug naïve patients.

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Glucagon-like peptide–1 and candesartan additively improve glucolipotoxicity in pancreatic β-cells

Cited by 38 publications

References 53 publications

GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways

GLP-1 promotes angiogenesis in human endothelial cells in a dose-dependent manner, through the Akt, Src and PKC pathways

Angiotensin receptor blockers: Focus on cardiac and renal injury

Dipeptidyl peptidase-4 inhibitor sitagliptin improves pancreatic β-cell function in hypertensive diabetic patients treated with angiotensin receptor blockers

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