scholarly journals Glucagon-Like Peptide-1 Receptor Agonist, Liraglutide, Attenuated Diabetic Retinal Edema in Spontaneously Diabetic Torii Fatty Rats

2021 ◽  
Author(s):  
Kazuho Inoue ◽  
Shohei Yamada ◽  
Seiko Hoshino ◽  
Minoru Watanabe ◽  
Kenjiro Kimura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Receptor Agonist ◽  
Vehicle Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Retinal Edema ◽  
Monocyte Chemoattractant Protein 1 ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background: This study aims to investigate the effect of the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide on retinal edema as compared with insulin and hydralazine using an animal model of type 2 diabetes with obesity, hypertension, and hyperlipidemia.Methods: Male spontaneously diabetic Torii (SDT) fatty rats at 8 weeks of age were randomly assigned to three groups: the liraglutide group (SDT-lira, n = 6) received a subcutaneous injection of liraglutide from the age of 8 to 16 weeks, the SDT-ins-hyd group (n = 6) was provided both insulin against hyperglycemia and hydralazine against hypertension to match levels of both blood glucose and blood pressure to those of the liraglutide group, and the control group of SDT fatty rats (SDT-vehicle, n = 7) and a nondiabetic control group of Sprague–Dawley rats (SD, n = 7) were injected with vehicle only. Both eyeballs of all groups were collected at the age of 16 weeks.Results: Retinal thickness, which was found in the SDT-vehicle group, was significantly prevented to similar levels in both the SDT-lira and SDT-ins-hyd groups. Immunohistological analysis revealed that GLP-1 receptor was not expressed in the retina of all rats. The ocular protein expression of monocyte chemoattractant protein-1, which causes a proinflammatory situation, was significantly upregulated in all SDT fatty rats as compared to SD rats, but the expression levels were similar between all SDT fatty rats. With regard to neovascularization in the eyes, there were no significant differences in protein expressions of vascular endothelial growth factor, CD31, or endothelial nitric oxide synthase in all rats.Conclusions: The present study indicates that liraglutide prevents retinal thickening, dependent on blood glucose and blood pressure levels in SDT fatty rats without ocular neovascularization. However, the effects did not improve the ocular proinflammatory state.

scholarly journals Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Noritaka Sawada ◽  
Kei Adachi ◽  
Nobuhisa Nakamura ◽  
Megumi Miyabe ◽  
Mizuho Ito ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Alveolar Bone ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Second Molar ◽  
Sd Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague–Dawley (SD) rats ( n = 30 ) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

[OP.4A.09] THE EFFECT OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST LIRAGLUTIDE ON 24-H BLOOD PRESSURE VARIATION

2016 ◽  
Vol 34 ◽  
pp. e42-e43 ◽  
Author(s):  
P. Kumarathurai ◽  
C. Anholm ◽  
O.K. Kristiansen ◽  
O.W. Nielsen ◽  
S.B. Haugaard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Receptor Agonist ◽  
Pressure Variation ◽  
Blood Pressure Variation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

951-P: Cotadutide (MEDI0382), a Dual Receptor Agonist with Glucagon-Like Peptide-1 and Glucagon Activity, Is Well Tolerated (<600 µG) with Robust Effects on Blood Glucose in Patients with T2DM

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 951-P
Author(s):  
DARREN ROBERTSON ◽  
LARS HANSEN ◽  
MEENA JAIN ◽  
VICTORIA PARKER ◽  
MARCELLA PETRONE ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Receptor Agonist ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Exendin-4, a Glucagon-Like Peptide-1 Receptor Agonist, Provides Neuroprotection in Mice Transient Focal Cerebral Ischemia

2011 ◽  
Vol 31 (8) ◽  
pp. 1696-1705 ◽  
Author(s):  
Shinichiro Teramoto ◽  
Nobukazu Miyamoto ◽  
Kenji Yatomi ◽  
Yasutaka Tanaka ◽  
Hidenori Oishi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Receptor Agonist ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Intracellular Camp ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Camp Levels

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia–reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.

scholarly journals Impact of glucagon like peptide-1 receptor agonist and sodium glucose cotransporter 2 inhibitors on type 2 diabetes patients with renal impairment

2020 ◽  
Vol 17 (6) ◽  
pp. 147916412097122
Author(s):  
Takeyuki Hiramatsu ◽  
Hiroki Ito ◽  
Shota Okumura ◽  
Yuko Asano ◽  
Daiki Iguchi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Renal Function ◽  
Renal Impairment ◽  
Cardiac Function ◽  
Receptor Agonist ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. Materials and methods: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)—dapagliflozin ( n = 52) or empagliflozin ( n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. Results: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups ( p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e′ or left atrial volume index, decreased only in Group G at 36 months. Conclusions: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.

scholarly journals The glucagon-like peptide 1 receptor agonist liraglutide attenuates placental ischemia-induced hypertension

2020 ◽  
Vol 318 (1) ◽  
pp. H72-H77
Author(s):  
Subhi Talal Younes ◽  
Kenji J. Maeda ◽  
Jennifer Sasser ◽  
Michael J. Ryan
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Nitric Oxide Synthase ◽  
Rat Model ◽  
Receptor Agonist ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Oxide Synthase ◽  
Placental Ischemia

Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic perturbations of nitric oxide function, reflective of generalized endothelial dysfunction. Therapies that target the nitric oxide pathway have shown promise in both clinical and preclinical studies of preeclampsia. The glucagon-like peptide 1 agonists have been shown to increase nitric oxide and lower blood pressure in patients with diabetes, in part, through activation of nitric oxide synthase (NOS). Therefore, we hypothesized that a direct acting glucagon-like peptide 1 receptor agonist would improve stigmata of the preeclampsia syndrome. Using the reduced uterine perfusion pressure rat model, we found that treatment with liraglutide significantly lowered blood pressure, improved renal function, and upregulated NOS3 protein expression in the mesenteric arterial bed. However, there were adverse effects on pup growth that were likely related to diminished food intake in the dams. Collectively, these data support the premise that the use of drugs that improve NOS abundance, including the glucagon-like peptide 1 agonists, is a rational therapeutic approach to the treatment of preeclampsia, but suggest cautious and careful study of their safety before potential clinical use in humans. NEW & NOTEWORTHY Drugs that target the glucagon-like peptide-1 pathway such as liraglutide are already used clinically, and it has been shown to promote endothelial nitric oxide synthase (NOS3) expression. We demonstrate that liraglutide, a glucagon-like peptide 1 receptor (GLP-1R) agonist, lowers blood pressure, improves renal function, and upregulates NOS3 in a rat model of placental ischemia. These data suggest that drugs that target the nitric oxide system, including GLP-1R agonists, are a potential therapeutic option for preeclampsia.

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