scholarly journals Glucagon-Like Peptide-1 Analog Liraglutide Protects against Diabetic Cardiomyopathy by the Inhibition of the Endoplasmic Reticulum Stress Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jieyu Liu ◽  
Yu Liu ◽  
Li Chen ◽  
Yuehui Wang ◽  
Junqi Li
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Caspase 12 ◽  
Before And After ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Endoplasmic Reticulum Stress Pathway ◽  
Stress Pathway

Aim. This study aimed to investigate whether the glucagon-like peptide-1 analog liraglutide (LIRA) can protect against diabetic cardiomyopathy and explore the related mechanism.Methods. Rats were divided into 6 groups: a nondiabetic group, diabetic cardiomyopathy rats without LIRA treatment, diabetic cardiomyopathy rats with LIRA treatment (with high-, medium-, and low-dose, resp.), and diabetic cardiomyopathy rats treated with insulin. Cardiac function was examined by echocardiography before and after treatment. The histopathology of the heart was examined with H&E staining. The mRNA levels of XBP1, ATF4, and TRAF2 were analyzed by RT-PCR, and the expression of glucose-regulated protein 78 (Grp78), enhancer-binding protein homologous protein (CHOP), caspase-3, and caspase-12 was detected by western blot.Results. LIRA strongly improved cardiac function from both echocardiographic and histopathologic analyses, but insulin only partly increased cardiac function by improving FS and LVPW values. LIRA treatment can significantly decrease the expression of XBP1, ATF4, and TRAF2 (P<0.01). LIRA also significantly downregulates the expression of Grp78, caspase-3 (P<0.01), CHOP, and caspase-12 (P<0.05).Conclusions. LIRA can protect against diabetic cardiomyopathy by inactivating the ER stress pathway. The improvement in cardiac function by LIRA is independent of glucose control.

scholarly journals The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

2017 ◽  
Vol 41 (6) ◽  
pp. 2503-2512 ◽  
Author(s):  
Yang Zhou ◽  
Wei Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Diabetic Cardiomyopathy ◽  
Left Ventricular ◽  
High Dose ◽  
Mrna Levels ◽  
Caspase 12 ◽  
Endoplasmic Reticulum Stress Pathway ◽  
Systolic And Diastolic Function ◽  
Stress Pathway

Background/Aims: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. Methods: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function. The histopathology of the heart was examined with hematoxylin-eosin staining. Expression of glucose-regulated protein (GRP)78, enhancer-binding protein homologous protein (CHOP), and caspase-12 was detected by Western blot, and the mRNA levels of XBP1, ATF4, and TRAF2 were analysed by real-time PCR. Results: EMPA significantly decreased the blood glucose level when compared with vehicle. EMPA strongly improved cardiac function based on hemodynamic and histopathologic analyses. Moreover, EMPA can significantly down-regulate the expression of GRP78, CHOP, and caspase-12 (P < 0.01). Additionally, the mRNA levels of XBP1, ATF4, and TRAF2 were markedly decreased by administration of EMPA (P < 0.01). Conclusion: EMPA protects against DCM by inactivating the endoplasmic reticulum stress pathway.

scholarly journals The deletion of glucagon-like peptide-1 receptors expressing neurons in the dorsomedial hypothalamic nucleus disrupts the diurnal feeding pattern and induces hyperphagia and obesity

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuko Maejima ◽  
Shoko Yokota ◽  
Masaru Shimizu ◽  
Shoichiro Horita ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Physiological Role ◽  
Feeding Pattern ◽  
Hypothalamic Nucleus ◽  
Acid Decarboxylase ◽  
Mrna Levels ◽  
Dorsomedial Hypothalamic Nucleus ◽  
Fos Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Background Feeding rhythm disruption contributes to the development of obesity. The receptors of glucagon-like peptide-1 (GLP-1) are distributed in the wide regions of the brain. Among these regions, GLP-1 receptors (GLP-1R) are expressed in the dorsomedial hypothalamic nucleus (DMH) which are known to be associated with thermogenesis and circadian rhythm development. However, the physiological roles of GLP-1R expressing neurons in the DMH remain elusive. Methods To examine the physiological role of GLP-1R expressing neurons in the DMH, saporin-conjugated exenatide4 was injected into rat brain DMH to delete GLP-1R-positive neurons. Subsequently, locomotor activity, diurnal feeding pattern, amount of food intake and body weight were measured. Results This deletion of GLP-1R-positive neurons in the DMH induced hyperphagia, the disruption of diurnal feeding pattern, and obesity. The deletion of GLP-1R expressing neurons also reduced glutamic acid decarboxylase 67 and cholecystokinin A receptor mRNA levels in the DMH. Also, it reduced the c-fos expression after refeeding in the suprachiasmatic nucleus (SCN). Thirty percent of DMH neurons projecting to the SCN expressed GLP-1R. Functionally, refeeding after fasting induced c-fos expression in the SCN projecting neurons in the DMH. As for the projection to the DMH, neurons in the nucleus tractus solitarius (NTS) were found to be projecting to the DMH, with 33% of those neurons being GLP-1-positive. Refeeding induced c-fos expression in the DMH projecting neurons in the NTS. Conclusion These findings suggest that GLP-1R expressing neurons in the DMH may mediate feeding termination. In addition, this meal signal may be transmitted to SCN neurons and change the neural activities.

scholarly journals Glucagon-like peptide-1 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the PPARα pathway

Aging Cell ◽  
2018 ◽  
Vol 17 (4) ◽  
pp. e12763 ◽  
Author(s):  
Lujin Wu ◽  
Ke Wang ◽  
Wei Wang ◽  
Zheng Wen ◽  
Peihua Wang ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Cardiac Lipotoxicity

GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats

2009 ◽  
Vol 297 (4) ◽  
pp. G663-G671 ◽  
Author(s):  
Tohru Hira ◽  
Taisuke Mochida ◽  
Kyoko Miyashita ◽  
Hiroshi Hara
Keyword(s):  
Small Intestine ◽  
Sampling Method ◽  
Rat Intestine ◽  
Mesenteric Vein ◽  
L Cells ◽  
Corn Protein ◽  
Before And After ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dose Dependent

Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small intestine. The duodenal, jejunal, and ileal administration of ZeinH induced dose-dependent increases in portal GLP-1 concentration. GLP-1 secretion in response to the ileal administration of ZeinH was higher than that in the duodenal or jejunal administration. Capsaicin treatment on esophageal vagal trunks abolished the GLP-1 secretion induced by duodenal ZeinH but did not affect the secretion induced by jejunal or ileal ZeinH. These results suggest that ZeinH in the jejunum or ileum directly stimulates GLP-1 secretion but duodenal ZeinH indirectly stimulates GLP-1 secretion via the vagal afferent nerve. A direct blood sampling method from the duodenal vein and ileal mesenteric vein revealed that ZeinH administered into the ligated duodenal loop enhanced GLP-1 concentration in the ileal mesenteric vein but not in the duodenal vein. This confirmed that ZeinH in the duodenum induces GLP-1 secretion from L cells located in the ileum by an indirect mechanism. These results indicate that a potent GLP-1-releasing peptide, ZeinH, induces GLP-1 secretion by direct and indirect mechanisms in the rat intestine.

scholarly journals GW26-e0013 The effect and mechanism of Glucagon-like peptide-1 protects against the diabetic cardiomyopathy

2015 ◽  
Vol 66 (16) ◽  
pp. C97
Author(s):  
Qinan Wu ◽  
Xiaotian Lei ◽  
Xiaguang Gan ◽  
Wuquan Deng ◽  
Bing Chen ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-Like Peptide-1 (GLP-1) Reduces Mortality and Improves Lung Function in a Model of Experimental Obstructive Lung Disease in Female Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4503-4511 ◽  
Author(s):  
Niels-Erik Viby ◽  
Marie S. Isidor ◽  
Katrine B. Buggeskov ◽  
Steen S. Poulsen ◽  
Jacob B. Hansen ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Whole Body ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Female Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P &lt; .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P &lt; .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

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