Sulforaphane Attenuation of Type 2 Diabetes-Induced Aortic Damage Was Associated with the Upregulation of Nrf2 Expression and Function

Type 2 diabetes mellitus (T2DM) significantly increases risk for vascular complications. Diabetes-induced aorta pathological changes are predominantly attributed to oxidative stress. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cytoprotective responses to oxidative stress. Sulforaphane protects against oxidative damage by increasing Nrf2 expression and its downstream target genes. Here we explored the protective effect of sulforaphane on T2DM-induced aortic pathogenic changes in C57BL/6J mice which were fed with high-fat diet for 3 months, followed by a treatment with streptozotocin at 100 mg/kg body weight. Diabetic and nondiabetic mice were randomly divided into groups with and without 4-month sulforaphane treatment. Aorta of T2DM mice exhibited significant increases in the wall thickness and structural derangement, along with significant increases in fibrosis (connective tissue growth factor and transforming growth factor), inflammation (tumor necrosis factor-αand vascular cell adhesion molecule 1), oxidative/nitrative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal), apoptosis, and cell proliferation. However, these pathological changes were significantly attenuated by sulforaphane treatment that was associated with a significant upregulation of Nrf2 expression and function. These results suggest that sulforaphane is able to upregulate aortic Nrf2 expression and function and to protect the aorta from T2DM-induced pathological changes.

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Faculty Opinions recommendation of Circulating bone morphogenetic protein-7 and transforming growth factor-β1 are better predictors of renal end points in patients with type 2 diabetes mellitus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717973821.793472703 ◽

2013 ◽

Author(s):

Mai Ots-Rosenberg

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Growth Factor ◽

Bone Morphogenetic Protein ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Bone Morphogenetic Protein 7 ◽

Morphogenetic Protein

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Clinical and pathogenetic features of intestinal lesions in patients with type 2 diabetes mellitus

Modern Gastroenterology ◽

10.30978/mg-2021-5-30 ◽

2021 ◽

Author(s):

Y. Z. Dynia

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Growth Factor ◽

Proinflammatory Cytokines ◽

Transforming Growth Factor ◽

Clinical Manifestations ◽

Intestinal Damage ◽

Hydrogen Breath Test

Objective — to study the incidence and clinical and pathogenetic features of intestinal injury in patients with type 2 diabetes mellitus. Materials and methods. Examinations involved 138 patients with type 2 diabetes mellitus (DM 2), aged from 39 to 67 years (mean age 53 ± 5 years), including 82 women (59 %) and 56 men (41 %). In addition to general clinical methods, investigations included plasma levels of the transforming growth factor‑b1 (TGF‑b1) and vascular endothelial growth factor (VEGF), the hydrogen breath test with lactulose, endoscopic examination of the intestine with biopsy followed by staining with hematoxylin‑eosin, immunohistochemical determining of claudin‑1 and VEGF, and conduction of PAS‑reaction. Results. Diabetic enterocolopathy (DECP) was diagnosed in 72 (52.2 %) patients with DM 2. Clinical manifestations were nonspecific and similar to those of irritable bowel syndrome (IBS). It has been found that DECP correlates with the duration of the DM 2 course and was diagnosed more often in middle‑aged patients (52.1 ± 4.1 years). In patients with DECP, the increase in the proinflammatory cytokines TGF‑b1 and VEGF significantly exceeded those in IBS patients. Histologically the inflammatory cell infiltration in patients with DECP was more intense and diverse, there were signs of subatrophy of the glands with a relative decrease in the number of vacuoles in the goblet cells. The immunohistochemical study revealed that VEGF in the colon mucosa was visualized mainly in patients with DECP. Moreover, a tendency to a decrease in the claudin‑1 levels was established in these patients. Conclusions. Intestinal damage was revealed in 67.4 % of patients with type 2 diabetes mellitus, and DECP was diagnosed in more than half of patients. Diabetic enterocolopathy had nonspecific clinical symptoms, required differential diagnosis with IBS, and was not always accompanied with abdominal pain. The presence of DECP more often correlated with the bacterial overgrowth syndrome, and levels of proinflammatory cytokines in the blood plasma and intestinal mucosa of these patients was raised.

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Study of serum transforming growth factor-beta 1 (TGF-?1) levels in type 2 diabetes mellitus patients with nephropathy

Biomedical Research ◽

10.4066/biomedicalresearch.29-18-950 ◽

2018 ◽

Vol 29 (16) ◽

Cited By ~ 1

Author(s):

Avanish Shukla ◽

Pawan Kumar Kare ◽

Basu Dev Banerjee ◽

Om Prakash Kalra ◽

Alpana Raizada ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Growth Factor Beta

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The Effect of Combination Therapy with Melatonin on the Enzymes of Glutathione System and the Level of Transforming Growth Factor- β1 in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

The Russian Archives of Internal Medicine ◽

10.20514/2226-6704-2021-11-5-359-369 ◽

2021 ◽

Vol 11 (5) ◽

pp. 359-369

Author(s):

S. S. Popov ◽

E. I. Anufrieva ◽

E. D. Kryl’skii ◽

A. N. Verevkin ◽

K. K. Shulgin

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Lipid Profile ◽

Antioxidant System ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Glutathione Antioxidant System

Aim. The aim of the work was to assess the effect of combination therapy with melatonin on the clinical and biochemical parameters of chronic kidney disease (CKD) and type 2 diabetes mellitus (DM), the level of transforming growth factor-β1, lipid profile, activity of the glutathione antioxidant system enzymes and the activity of NADPH-generating enzymes in patients.Materials and methods. The study involved 60 people (19 men and 41 women, average age 65.6 ± 9.3 years) with chronic kidney disease associated with type 2 diabetes. The patients were divided into 2 groups. The first group of patients received basic treatment (n = 30, 8 men and 22 women, mean age 64.1 ± 7.9 years); the second group of participants (n = 30, 11 men and 19 women, mean age 69.0 ± 10.5 years) received 2 mg of melatonin in addition to the basic therapy. The control group consisted of 65 apparently healthy individuals (30 men and 35 women, average age 42.3±17.7 years) with normal indicators of general and biochemical blood tests. In the course of the work, the analysis of clinical and biochemical indicators and lipid profile in blood serum, the level of transforming growth factor-β1 by enzyme immunoassay, the activity of enzymes of the glutathione antioxidant system and NADPH-generating enzymes by the spectrophotometric method were carried out.Results. The use of melatonin additionally with basic treatment compared with standard therapy led to a decrease in proteinuria (p=0.010), hyperglycemia (p=0.019), urea concentration (p=0.043), glycated hemoglobin (p=0.045) and transforming growth factor-β1 levels (p=0.020) in patients with CKD. In addition, the use of this drug led to a changing of the lipid profile, and the activity of glutathione antioxidant system enzymes and NADPH-generating enzymes.Conclusion. The differences observed during the study were apparently caused by the action of melatonin, which has nephroprotective and hypoglycemic properties, the ability to neutralize reactive oxygen species and activate the antioxidant system functioning.

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