Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof

Fisman, Enrique Z.; Motro, Michael; Tenenbaum, Alexander

doi:10.1186/1475-2840-2-11

Cited by 41 publications

(15 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammation also is involved in many of the metabolic abnormalities associated with diabetes, the most important of them being insulin resistance [3, 9]. …”

Section: Introductionmentioning

confidence: 99%

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study

Younis

Eskenazi

Goldkorn

et al. 2017

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

BackgroundPatients with type 2 diabetes present with an accelerated atherosclerotic process. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors (gliptins) have anti-inflammatory and anti-atherosclerotic effects, yet clinical data are scarcely available.Design and methodsA prospective, randomized, open-label study was performed in 60 patients with coronary artery disease (CAD) and type 2 diabetes, who participated in a cardiac rehabilitation program. After a washout period of 3 weeks, patients were randomized in a 2:1 ratio to receive combined vildagliptin/metformin therapy (intervention group: n = 40) vs. metformin alone (control group: n = 20) for a total of 12 weeks. Blinded assessment of interleukin-1ß (IL-1ß, the primary endpoint), hemoglobin A1c (HbA1c), and high sensitivity C reactive protein (hsCRP), were performed at baseline and after 12 weeks.ResultsMean age of study patients was 67 ± 9 years, 75% were males, and baseline HbA1c and inflammatory markers levels were similar between the two groups. At 12 weeks of follow up, levels of IL-1ß, hsCRP, and HbA1c were significantly lower in the intervention group as compared with the control group. There was a continuous elevation of IL-1ß among the control group, which was not observed in the intervention group (49 vs. 4%, respectively; p < 0.001). The hsCRP was lowered by 60% in the vildagliptin/metformin group vs. 23% in the metformin group (p < 0.01). Moreover, a significant relative reduction of the HbA1c was seen in the intervention group (7% reduction, p < 0.03).ConclusionThe addition of vildagliptin to metformin treatment in patients with type 2 diabetes and CAD led to a significant suppression of the IL-1ß elevation during follow up. A significant relative reduction of hsCRP and HbA1c in the intervention group was also observed. Trial registration NCT01604213Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0551-5) contains supplementary material, which is available to authorized users.

show abstract

“…Inflammation also is involved in many of the metabolic abnormalities associated with diabetes, the most important of them being insulin resistance [3, 9]. …”

Section: Introductionmentioning

confidence: 99%

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study

Younis

Eskenazi

Goldkorn

et al. 2017

Cardiovasc Diabetol

Self Cite

View full text Add to dashboard Cite

show abstract

“…IL-10 is considered an anti-inflammatory cytokine with a potentially protective actions against development of both endothelial dysfunction and atherosclerosis [5]. Increased IL-10 circulating levels are thus emerging as a potential protective factor.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, circulating pro-inflammatory cytokines, such as Tumor necrosis factor (TNF)-α and interleukine-6 (IL-6), are elevated in obese subjects [2], while plasma levels of anti-inflammatory cytokines, such as interleukine-10 (IL-10), appear to be reduced [3]. Diet-induced weight loss is accompanied by an inflammatory cytokines decrease [4], [5] and by an IL-10 increase in plasma [6].…”

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Imaging Determined Visceral Fat Reduction Associates with Enhanced IL-10 Plasma Levels in Calorie Restricted Obese Subjects

et al. 2012

View full text Add to dashboard Cite

BackgroundObesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI) protocol before and after weight loss.Materials and MethodsIn 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight.ResultsWeight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05), increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03), and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively). A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05) and IL-6 (r = 0.19 p<0.05) plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels.ConclusionThe reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

show abstract

“…Inflammatory mechanisms, including oxidative stress and cytokine productions have been proposed to participate in the cardiovascular diabetic complication 23–25 . Treatment with STZ increased mortality rate in both WT and TRPC6 (−/−) mice compared to TRPC3 (−/−) mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Oda

Numaga‐Tomita

Kitajima

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.

show abstract

Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof

Cited by 41 publications

References 81 publications

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study

The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study

Magnetic Resonance Imaging Determined Visceral Fat Reduction Associates with Enhanced IL-10 Plasma Levels in Calorie Restricted Obese Subjects

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice

Contact Info

Product

Resources

About