Role of diabetic autonomic neuropathy in development of diabetic cardiomyopathy in patients with diabetes

Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which results in cardiac hypertrophy and subsequent heart failure. Chronic inflammation in the diabetic heart results in loss of cardiomyocytes and subsequentially cardiac dysfunction. Accumulated evidence implicated pyroptosis as a vital contributor to the hyperglycemia-induced cardiac inflammatory response. Exendin-4, a GLP analog, promotes survival of cardiomyocytes in cardiovascular diseases, including diabetic cardiomyopathy. However, the role of Exendin-4 in cardiac pyroptosis remains to be elucidated. Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats. The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well. In an effort to understand the signaling mechanisms underlying the antipyroptotic property of Exendin-4, we found that blockade of AMPK, an oxidative stress sensor, activity diminished the antipyroptotic property of Exendin-4. Phosphorylation of AMPK resulted in degeneration of TXNIP that promoted the activation of the NLRP3 inflammasome. Exendin-4 treatment decreased the protein level of TXNIP. Moreover, RNA silencing of TXNIP mimicked the antipyroptotic actions of Exendin-4. These findings promoted us to propose a new signaling pathway mediating cardioprotective effect of Exendin-4 under hyperglycemic conditions: Exendin-4 → ROS↓ → pAMPK↑ → TXNIP↓ → caspase-1↓ → IL-1β and IL-18↓ → pyroptosis↓. In general, our study identified Exendin-4 as a pyroptotic inhibitor protecting against hyperglycemia-induced cardiomyocyte pyroptosis via the AMPK-TXNIP pathway.

Download Full-text

Role of Microcirculatory Disturbances and Diabetic Autonomic Neuropathy in Takotsubo Cardiomyopathy

Critical Care Medicine ◽

10.1097/ccm.0000000000001183 ◽

2015 ◽

Vol 43 (11) ◽

pp. e527 ◽

Cited By ~ 12

Author(s):

Nauman Khalid ◽

Sarah Aftab Ahmad ◽

Affan Umer ◽

Lovely Chhabra

Keyword(s):

Autonomic Neuropathy ◽

Takotsubo Cardiomyopathy ◽

Diabetic Autonomic Neuropathy ◽

Microcirculatory Disturbances

Download Full-text

Mechanisms and Therapeutic Prospects of Diabetic Cardiomyopathy Through the Inflammatory Response

Frontiers in Physiology ◽

10.3389/fphys.2021.694864 ◽

2021 ◽

Vol 12 ◽

Author(s):

Namrita Kaur ◽

Yingshu Guan ◽

Rida Raja ◽

Andrea Ruiz-Velasco ◽

Wei Liu

Keyword(s):

Diabetic Cardiomyopathy ◽

Systolic Dysfunction ◽

Clinical Complications ◽

Cytokines And Chemokines ◽

Patients With Diabetes ◽

Potential Benefits ◽

Artery Disease ◽

The Impact ◽

Precise Role

The incidence of heart failure (HF) continues to increase rapidly in patients with diabetes. It is marked by myocardial remodeling, including fibrosis, hypertrophy, and cell death, leading to diastolic dysfunction with or without systolic dysfunction. Diabetic cardiomyopathy (DCM) is a distinct myocardial disease in the absence of coronary artery disease. DCM is partially induced by chronic systemic inflammation, underpinned by a hostile environment due to hyperglycemia, hyperlipidemia, hyperinsulinemia, and insulin resistance. The detrimental role of leukocytes, cytokines, and chemokines is evident in the diabetic heart, yet the precise role of inflammation as a cause or consequence of DCM remains incompletely understood. Here, we provide a concise review of the inflammatory signaling mechanisms contributing to the clinical complications of diabetes-associated HF. Overall, the impact of inflammation on the onset and development of DCM suggests the potential benefits of targeting inflammatory cascades to prevent DCM. This review is tailored to outline the known effects of the current anti-diabetic drugs, anti-inflammatory therapies, and natural compounds on inflammation, which mitigate HF progression in diabetic populations.

Download Full-text

Prevention of Diabetic Complications by Activation of Nrf2: Diabetic Cardiomyopathy and Nephropathy

Experimental Diabetes Research ◽

10.1155/2012/216512 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 63

Author(s):

Bing Li ◽

Shujun Liu ◽

Lining Miao ◽

Lu Cai

Keyword(s):

Diabetic Cardiomyopathy ◽

Diabetic Complications ◽

Protective Action ◽

Redox Status ◽

Diabetic Patients ◽

Related Factor ◽

Oxidative Stresses ◽

Cellular Detoxification ◽

Patients With Diabetes

Diabetic cardiomyopathy and nephropathy are two major causes of death of patients with diabetes. Extra generation of reactive oxygen species (ROS), induced by hyperglycemia, is considered as the main reason for the development of these diabetic complications. Transcription factor, NFE2-related factor 2 (Nrf2), is a master regulator of cellular detoxification response and redox status, and also provides a protective action from various oxidative stresses and damages. Recently we have demonstrated its important role in determining the susceptibility of cells or tissues to diabetes-induced oxidative stress and/or damage. Therefore, this review will specifically summarize the information available regarding the effect of Nrf2 on the diabetic complications with a focus on diabetic cardiomyopathy and nephropathy. Given the feature that Nrf2 is easily induced by several compounds, we also discussed the role of different Nrf2 activators in the prevention or therapy of various diabetic complications. These findings suggest that Nrf2 has a potential application in the clinic setting for diabetic patients in the short future.

Download Full-text

Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling

Biological Chemistry ◽

10.1515/bc.2008.082 ◽

2008 ◽

Vol 389 (6) ◽

Cited By ~ 9

Author(s):

Carsten Tschöpe ◽

Dirk Westermann

Keyword(s):

Diabetic Cardiomyopathy ◽

Calcium Handling ◽

Kinin System ◽

Cardiac Inflammation ◽

B1 Receptor ◽

Kinin Receptors ◽

Patients With Diabetes ◽

Underlying Mechanisms ◽

Kallikrein Kinin System

Abstract Diabetic cardiomyopathy is a specific cardiomyopathy which develops in patients with diabetes mellitus in the absence of coronary atherosclerosis and hypertension. Despite the potential importance of this disease entity, the underlying mechanisms are only incompletely understood. Changes in calcium handling, disruption of the extracellular matrix regulation with accumulation of cardiac collagen, and furthermore cardiac inflammation may be an important mediator of this disease. This brief review focuses on the current aspects of the kallikrein-kinin system and its influence on the development of diabetic cardiomyopathy with particular regard to the kinin receptors B1 and B2, as their role in the development of this disease is still under discussion. Whether the role of the B1 receptor is similar to the well-described beneficial role of the B2 receptor or whether its function is opposed to the B2 receptor is controversial. Some recent findings suggest that the B1 receptor mediates cardiac inflammation and therefore may be detrimental for cardiac function in the setting of diabetic cardiomyopathy.

Download Full-text

Diabetic autonomic neuropathy as a risk factor for emergencies

Kazan medical journal ◽

10.17750/kmj2016-931 ◽

2016 ◽

Vol 97 (6) ◽

pp. 931-934 ◽

Cited By ~ 1

Author(s):

T G Sakovets

Keyword(s):

Autonomic Neuropathy ◽

Clinical Manifestations ◽

Vascular Complications ◽

Endocrine System ◽

Nerve Fibers ◽

Diabetic Autonomic Neuropathy ◽

Autonomic Nerve ◽

Organ Systems ◽

Patients With Diabetes

Diabetic autonomic neuropathy includes damage of various organ systems. The manifestations of autonomic neuropathy usually occur in setting of distal sensory motor polyneuropathy but autonomic disorders may be presented disproportionately compared to sensory and motor disorders. Diabetic autonomic neuropathy increases the risk of cardiac arrhythmias and sudden death, significantly reduces the patients’ quality of life, and exacerbates other vascular complications of diabetes mellitus. There are cardiovascular, gastrointestinal and urogenital forms of diabetic autonomic neuropathy and damaged function of autonomic nerve fibers involving respiratory system, pupils, sudoriferous glands, thermoregulatory and endocrine system. Cardiovascular autonomic neuropathy is the most studied, clinically meaningful and prognostically pejorative form of autonomic neuropathy. Autonomous diabetic neuropathy can cause frequent emergency admissions of patients with this pathology, increased mortality in patients with diabetes, which requires informing of general practitioners, endocrinologists, and intensivists about the features of the clinical manifestations and course of this disease.

Download Full-text