Insulin Suppresses Type 1 Diabetes Mellitus-Induced Ventricular Cardiomyocyte Damage Associated with the Inhibition of Biomarkers of Inflammation and Oxidative Stress in Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 157-165 ◽  
Author(s):  
Mohammad Dallak ◽  
Bahjat Al-Ani ◽  
Dina H. Abdel Kader ◽  
Refaat A. Eid ◽  
Mohamed A. Haidara
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Serum Levels ◽  
Left Ventricular ◽  
Daily Injection ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

Aims: We sought to determine whether insulin can protect against type 1 diabetes mellitus (T1DM)-induced cardiac ultrastructural alterations in an animal model of the disease. This has not been investigated before. Methods: Rats were either injected once with 65 mg/kg streptozotocin (STZ) before being sacrificed after 8 weeks or were treated with a daily injection of insulin 2 days by STZ and continued until being sacrificed. Results: Harvested tissues obtained from left ventricles in the untreated T1DM rats showed substantial damage to the cardiomyocyte ultrastructure as demonstrated by disintegrated myofibrils and their sarcomeres, damaged mitochondria and lipid droplets, which was substantially protected by insulin. Insulin also significantly inhibited T1DM-induced hyperglycemia (p < 0.001), dyslipidemia (p < 0.0001), malondialdehyde (MDA; p < 0.0001), tumor necrosis factor-alpha (TNF-α; p < 0.001) and interleukin-6 (p < 0.001). We further demonstrated a significant (p ≤ 0.001) correlation between either sarcomere or mitochondrial injury scoring and the serum levels of glucose, dyslipidemia, and biomarkers of oxidative stress (OxS) and inflammation. Conclusions: These results indicate that insulin effectively suppresses left ventricular cardiomyocyte ultrastructural damage, which substantially slows down the progression of diabetic cardiomyopathy for 8 weeks in a rat model of T1DM, possibly due to the glycemic control and inhibition of dyslipidemia, OxS and inflammation.

scholarly journals Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 752
Author(s):  
Aikaterini Kountouri ◽  
Emmanouil Korakas ◽  
Ignatios Ikonomidis ◽  
Athanasios Raptis ◽  
Nikolaos Tentolouris ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
B Cells ◽  
Type 1 Diabetes Mellitus ◽  
Pathophysiological Mechanism ◽  
Necrosis Factor Alpha ◽  
Angiotensin Converting Enzyme 2 ◽  
Life Threatening

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a “cytokine storm”. Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.

Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress

2008 ◽  
Vol 9 (2) ◽  
pp. 104-109 ◽  
Author(s):  
Raanan Shamir ◽  
Haifa Kassis ◽  
Marielle Kaplan ◽  
Tova Naveh ◽  
Naim Shehadeh
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Serum Levels ◽  
And Oxidative Stress

Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus

2011 ◽  
Vol 48 (12-13) ◽  
pp. 1397-1407 ◽  
Author(s):  
Paola I. Ingaramo ◽  
María T. Ronco ◽  
Daniel E.A. Francés ◽  
Juan A. Monti ◽  
Gerardo B. Pisani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Tumor Necrosis Factor ◽  
Type 1 Diabetes Mellitus ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

P620The prognostic value of the ratio of transmitral early filling velocity to early diastolic strain rate in type 1 diabetes patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M H Lassen ◽  
T B S Biering-Soerensen ◽  
P G J Joergensen ◽  
H U A Andersen ◽  
P R Rossing ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Prognostic Value ◽  
Left Ventricular ◽  
Morbidity And Mortality ◽  
Female Patients ◽  
Cardiovascular Morbidity And Mortality ◽  
Early Filling

Abstract Background Cardiovascular disease is one of the main causes of morbidity and mortality in patients suffering from type 1 diabetes mellitus. It is of great importance to identify early signs of cardiac pathology such as elevated left ventricular (LV) filling pressure. The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to be an accurate measure of left ventricular (LV) filling pressure. Furthermore, E/e'sr has demonstrated strong prognostic value across different study populations. Purpose The aim of this study was to assess the prognostic value of E/e'sr in a large cohort of patients with type 1 diabetes mellitus in relation to cardiovascular morbidity and mortality. Methods In this prospective study, 1082 patients with type 1 diabetes mellitus (mean age 50±15 years, 53% male, mean duration of diabetes 26 years) underwent a comprehensive echocardiographic examination including both conventional measurements and two-dimensional speckle tracking in which E/e'sr along with other echocardiographic measurements were obtained. The primary outcome was defined as a major cardiac event (heart failure, stroke, myocardial infarction or cardiovascular death). Results During follow-up (median: 6.2 years, IQR: 5.7, 6.9) 144 (13.3%) met the composite outcome. E/e'sr was significantly associated with the composite outcome (E/e'sr: HR 1.36 95% CI [1.25–1.47], p<0.001, per 0.10m increase) (figure). E/e'sr remained an independent predictor after multivariable adjustment for age, gender, duration of diabetes, BMI, HbA1c, smoking status, level of physical activity, systolic blood pressure, cholesterol level, eGFR, albuminuria, LV ejection fraction, LV dimensions and left atrial volume index (E/e'sr: HR 1.16 95% CI [1.04–1.28], p=0.006, per 0.10m increase). Interestingly, E/e'sr was especially good as a prognosticator in female patients (p for interaction = 0.008) in a univariable model: (female: HR 1.53 95% CI [1.37–1.71], p<0.001, per 0.10m increase) (male: HR 1.23 95% CI [1.10–1.38], p<0.001, per 0.10m increase). In the same multivariable model as before, E/e'sr remained an independent predictor of the outcome in female patients whereas the same was not true for male patients (female: HR 1.39 95% CI [1.18–1.66], p<0.001, per 0.10m increase) vs (male: HR 1.05 95% CI [0.92–1.21], p=0.46, per 0.10m increase). Conclusion In patients with type 1 diabetes, E/e'sr provides independent prognostic information regarding cardiovascular morbidity and mortality. Furthermore, E/e'sr seems to have stronger prognostic value in female patients with type 1 diabetes.

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