scholarly journals Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus

2019 ◽  
Vol 49 (4) ◽  
pp. 331-342 ◽  
Author(s):  
T. Cooper Woods ◽  
Ryousuke Satou ◽  
Kayoko Miyata ◽  
Akemi Katsurada ◽  
Courtney M. Dugas ◽  
...  

Background: Hypertension and renal injury are common complications of type 2 diabetes mellitus (T2DM). Hyperglycemia stimulates renal proximal tubular angiotensinogen (AGT) expression via elevated oxidative stress contributing to the development of high blood pressure and diabetic nephropathy. The sodium glucose cotransporter 2 (SGLT2) in proximal tubules is responsible for the majority of glucose reabsorption by renal tubules. We tested the hypothesis that SGLT2 inhibition with canagliflozin (CANA) prevents intrarenal AGT augmentation and ameliorates kidney injury and hypertension in T2DM. Methods: We induced T2DM in New Zealand obese mice with a high fat diet (DM, 30% fat) with control mice receiving regular fat diet (ND, 4% fat). When DM mice exhibited > 350 mg/dL blood glucose levels, both DM- and ND-fed mice were treated with 10 mg/kg/day CANA or vehicle by oral gavage for 6 weeks. We evaluated intrarenal AGT, blood pressure, and the development of kidney injury. Results: Systolic blood pressure in DM mice (133.9 ± 2.0 mm Hg) was normalized by CANA (113.9 ± 4.0 mm Hg). CANA treatment ameliorated hyperglycemia-associated augmentation of renal AGT mRNA (148 ± 21 copies/ng RNA in DM, and 90 ± 16 copies/ng RNA in DM + CANA) and protein levels as well as elevation of urinary 8-isoprostane levels. Tubular fibrosis in DM mice (3.4 ± 0.9-fold, fibrotic score, ratio to ND) was suppressed by CANA (0.9 ± 0.3-fold). Furthermore, CANA attenuated DM associated increased macrophage infiltration and cell proliferation in kidneys of DM mice. Conclusions: CANA prevents intrarenal AGT upregulation and oxidative stress and which may mitigate high blood pressure, renal tubular fibrosis, and renal inflammation in T2DM.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ilian Janet García-González ◽  
Yeminia Valle ◽  
Fernando Rivas ◽  
Luis Eduardo Figuera-Villanueva ◽  
José Francisco Muñoz-Valle ◽  
...  

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P≥0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65,P=0.02). The genetic recessive model showed similar findings (ORc = 3.03,P=0.04). No association was found in ACS, with aPof 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.


2012 ◽  
Vol 50 (5) ◽  
pp. 825-826
Author(s):  
Turgay Ulas ◽  
Mehmet Sinan Dal ◽  
Irfan Tursun ◽  
Mehmet Emin Demir ◽  
Hakan Buyukhatipoglu

2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 20-23 ◽  
Author(s):  
Cátia Ferreira da SILVA ◽  
Larissa COHEN ◽  
Luciana d'Abreu SARMENTO ◽  
Felipe Monnerat Marino ROSA ◽  
Eliane Lopes ROSADO ◽  
...  

ABSTRACT Background: Due to the high failure rate observed in the clinical treatment of morbid obesity an increase in bariatric surgery indications, as an alternative for the control of obesity and comorbidities, is noticeable. Aim: To evaluate the performance of type 2 diabetes mellitus, high blood pressure and dyslipidemia in patients submitted to Roux-en-Y gastric bypass in late follow-up. Methods: Retrospective analysis of 59 patients included in the bariatric surgery program. Anthropometric (height and body weight) and laboratory (LDLc, HDLc, VLDLc, triglyceride -TG - and glucose) data were collected on pre- and postoperative stages, through medical records. Results: Among the patients, 86% were female aged 43±11, of whom 52% had attended high school. The average postoperative time was 7±3 years. During the postoperative period, there were decreases of weight and body mass index, respectively (133±06 kg vs 91±04 kg p<0.05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0.05). In comparison to the preoperative stage, lower concentrations of glucose (101.00±26.99 vs 89,11±15.19, p=0.014), total cholesterol rates (179.00±37,95 vs 167.48±28,50, p=0.016), LDLc (104.30±33.12 vs 91.46±24.58, p=0.016), VLDLc (25.40±11,12 vs 15.68±7.40, p<0.01), and TG (143.35±86.35 vs 82.45±37.39, p<0.01) and higher concentrations of HDLc (43.53±8.23 vs 57.90±15.60, p<0.01) were identified in the postoperative stage. 40% of hypertensive patients were still undergoing high blood pressure treatment during the postoperative stage. There was remission of type 2 diabetes mellitus and dyslipidemia on 81% and 94% of the cases, respectively. Conclusion: Roux-en-Y gastric bypass has proven itself to be an effective long term procedure, promoting weight loss, remission of DM2 and dyslipidemia.


2018 ◽  
Vol 4 (3-4) ◽  
pp. 181-186
Author(s):  
Amit Singh ◽  
Padmini Tekur ◽  
Kashinath Metri ◽  
Hemant Bhargav ◽  
Nagarathna Raghuram ◽  
...  

Background: Type 2 diabetes mellitus (T2DM) is a highly prevalent disease characterized by chronic hyperglycemia. Yoga is a form of mind-body intervention shown to have a positive impact on several health conditions in both healthy and diseased patients. The present study is intended to assess the effects of the Residential Integrated Yoga Program (RIYP) on blood glucose levels in patients with T2DM. Material and Methods: Data of 598 (186 females) T2DM patients from a holistic health center in Bengaluru, India, who attended a 15-day RIYP between January 2013 and December 2015 was obtained retrospectively. Average age of the participants was 56.45 ± 11.02 years. All subjects underwent a 15-day RIYP which involved yoga-based lifestyle changes with components of regulated sleep, balanced diet, asanas, pranayama, relaxation techniques, meditations, yogic cleaning procedures, and tuning to the nature. Fasting and post-prandial blood sugar, medication score, symptom score, systolic and diastolic blood pressure, pulse rate, and respiratory rate were assessed before and after intervention. Result: There was a significant decrease in fasting (p < 0.001) and post-prandial blood sugar levels (p < 0.001) along with a significant reduction in medication and symptom scores after 15 days of RIYP compared to baseline. Conclusion: The present study indicates that 2 weeks of a yoga-based residential program improves blood glucose levels, blood pressure, and medication score in patients with T2DM. However, further randomized controlled studies need to be performed in order to confirm the present findings.


Sign in / Sign up

Export Citation Format

Share Document