Published online Dec 15, 2024. doi: 10.4239/wjd.v15.i12.2370
Revised: September 27, 2024
Accepted: October 29, 2024
Published online: December 15, 2024
Processing time: 251 Days and 4.1 Hours
This article provides commentary on the article by Zhang et al. In this original research, Zhang et al investigated the therapeutic potential of teneligliptin for diabetic cardiomyopathy (DCM), which was mediated by targeting the NOD-like receptor protein 3 (NLRP3) inflammasome. Through the use of both in vivo and in vitro models, the study demonstrated that teneligliptin alleviates cardiac hyper
Core Tip: Teneligliptin can mitigate diabetic cardiomyopathy (DCM) by inhibiting NOD-like receptor protein 3 inflammasome activation and upregulating AMP-activated protein kinase signaling. This study provides insights into the molecular mechanisms underlying the beneficial effects of teneligliptin for the treatment of DCM.
- Citation: Cheng CY, Hao WR, Liu JC, Cheng TH. Teneligliptin mitigates diabetic cardiomyopathy through inflammasome inhibition: Insights from experimental studies. World J Diabetes 2024; 15(12): 2370-2375
- URL: https://www.wjgnet.com/1948-9358/full/v15/i12/2370.htm
- DOI: https://dx.doi.org/10.4239/wjd.v15.i12.2370
Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus (DM); DCM is characterized by structural and functional abnormalities in the myocardium that often lead to heart failure[1]. The activation of inflammatory pathways, particularly those involving the NOD-like receptor protein 3 (NLRP3) inflammasome, plays a central role in the development of DCM and is closely associated with myocardial damage in patients with diabetes[2]. Teneligliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a promising therapeutic agent for DCM due to its anti-inflammatory and cytoprotective effects[3]. Zhang et al[4] demonstrated that teneligliptin protects against DCM by inhibiting NLRP3 inflammasome activation. Through in vivo and in vitro models, their study revealed that teneligliptin reduces cardiac hypertrophy, alleviates myocardial injury, and suppresses inflammatory pathways. In a streptozotocin-induced diabetic mouse model, teneligliptin considerably improved cardiac function and reduced the levels of myocardial damage markers[4], indicating its potential to address both the inflammatory and structural aspects of DCM. The rising global prevalence of diabetes and its complications, including DCM, indicates the urgent need for effective treatments. Zhang et al[4] indicated that targeting the NLRP3 inflammasome, a key mediator of inflammatory responses, is a novel therapeutic strategy. Teneligliptin, with its dual roles in glycemic control and preventing inflammation, has promising therapeutic potential for DCM[5]. Although these results are encouraging, further research is required to fully elucidate the mecha
DCM is a distinct form of heart disease that is directly associated with diabetes, and it is independent of other common cardiovascular risk factors, such as atherosclerosis and hypertension[1]. The diabetic state triggers several metabolic disturbances, including chronic hyperglycemia, insulin resistance, and dyslipidemia, which collectively drive the pathophysiology of DCM. These metabolic abnormalities lead to the increased production of reactive oxygen species (ROS), causing oxidative stress and damage to myocardial cells[2]. This oxidative stress initiates inflammation, a key factor in DCM progression. The persistent activation of the NLRP3 inflammasome, a multiprotein complex that detects cellular stress signals, is a crucial driver of this inflammatory response. Upon activation, the NLRP3 inflammasome promotes the release of proinflammatory cytokines, particularly interleukin (IL)-1β and IL-18[4]. These cytokines further increase inflammation, causing widespread myocardial damage and accelerating the progression toward heart failure. Chronic hyperglycemia and insulin resistance also contribute to structural abnormalities in the myocardium in DCM, such as myocardial fibrosis and hypertrophy[6]. Fibrosis, which is characterized by excessive collagen deposition in the myocardial extracellular matrix, leads to stiffening of the heart tissue and impaired contractility. Hypertrophy, or thi
The NLRP3 inflammasome plays a critical role in regulating inflammation, particularly in DCM, where its activation substantially accelerates disease progression. As a key sensor of pathogenic signals, the NLRP3 inflammasome is an essential component of the innate immune system. Under diabetic conditions, elevated glucose levels, mitochondrial dysfunction, and advanced glycation end-product accumulation[4] activate the NLRP3 inflammasome[4]. Once activated, the inflammasome mediates the cleavage and release of proinflammatory cytokines, including IL-1β and IL-18, which amplify inflammation and contribute to progressive myocardial damage[2]. Chronic activation of the NLRP3 inflammasome in the diabetic myocardium is closely linked to fibrosis, which is characterized by excessive extracellular matrix protein deposition; this causes structural remodeling and increased cardiac stiffness[1]. Persistent NLRP3 activity is also associated with pathological changes, including left ventricular hypertrophy, diastolic dysfunction, and eventual heart failure[2]. Inflammation driven by NLRP3 not only accelerates fibrosis but also impairs both systolic and diastolic cardiac functions, worsening the clinical manifestations of DCM[4]. Therapeutic strategies aimed at reducing NLRP3 activation could halt or slow the progression of DCM. Teneligliptin inhibits NLRP3 inflammasome activation and reduces inflammation in the diabetic heart[4]. Studies have demonstrated that teneligliptin reduces the release of IL-1β and IL-18, limits fibrosis, and improves both systolic and diastolic functions, indicating its potential cardioprotective effects for managing DCM[5,8]. In summary, the NLRP3 inflammasome forms a crucial link between metabolic disturbances and immune responses in DCM. Its chronic activation drives structural remodeling and functional decline in the heart. Pharmacological interventions targeting NLRP3, such as teneligliptin, offer significant potential for reducing inflammation and protecting against the progression of diabetic heart disease[1,4].
Teneligliptin is widely recognized for its ability to improve glycemic control in type 2 diabetes by enhancing incretin levels, which stimulate insulin secretion and reduce glucagon production[7]. Beyond its glucose-regulating effects, teneligliptin also exerts anti-inflammatory and cardioprotective effects, making it a promising therapeutic agent in DCM[6]. Recent studies have highlighted the role of teneligliptin in mitigating the activation of the NLRP3 inflammasome, a key mediator of inflammation in DCM[4]. Metabolic dysregulation in diabetes triggers NLRP3 inflammasome activation, leading to the release of proinflammatory cytokines, such as IL-1β and IL-18; these cytokines drive chronic inflammation and fibrosis in cardiac tissue, worsening structural remodeling and functional decline[2]. By inhibiting NLRP3 activation, teneligliptin reduces cytokine secretion and limits myocardial damage, effectively alleviating inflammation and preve
Teneligliptin inhibits NLRP3 inflammasome activation through multiple mechanisms involving oxidative stress and metabolic signaling pathways. A key mechanism involves the ability of teneligliptin to reduce oxidative stress by enha
Teneligliptin shows considerable promise for the treatment of DCM, which is primarily due to its anti-inflammatory properties. Although all DPP-4 inhibitors are effective for improving glycemic control, teneligliptin has additional car
Zhang et al[4] indicated that teneligliptin mitigates DCM by inhibiting the activation of the NLRP3 inflammasome. Thus, teneligliptin can address the unmet clinical needs of patients with diabetes. DCM, a leading cause of heart failure in diabetic individuals, has traditionally been managed with therapies aimed primarily at glycemic control and general cardiovascular protection. However, the progression of DCM is affected by inflammation, fibrosis, and mitochondrial dy
The safety profile of teneligliptin, as demonstrated in extensive post-marketing surveillance, indicates its potential as a long-term therapeutic option for patients with type 2 DM (T2DM) and cardiovascular complications[3]. Its safety across various patient subgroups, especially those with DCM and other comorbidities should be explored. Teneligliptin’s safety in patients with cardiovascular complications is particularly significant for individuals with DCM. Research, including that of Zhang et al[4], highlights the role of teneligliptin in mitigating DCM progression through the inhibition of the NLRP3 inflammasome, a critical mediator of inflammation and cardiac damage. This anti-inflammatory effect offers a dual advantage for patients managing both T2DM and cardiovascular conditions. The ARISE-HF trial’s baseline findings emphasize the complex relationship between diabetes and heart failure, further highlighting the need for therapies such as teneligliptin that may positively affect cardiac outcomes[1]. In addition to its cardiovascular benefits, teneligliptin’s safety in combination with other antidiabetic agents has been well-explored. The TOPLEVEL trial, for instance, demo
Zhang et al’s study significantly advances the understanding of the role of inflammation in the pathogenesis of DCM and establishes a foundation for future therapeutic research[4]. By highlighting that the activation of the NLRP3 inflammasome and associated inflammatory pathways are involved in the pathogenesis of DCM, this research indicates the critical importance of targeting inflammation to mitigate DCM progression[2,4]. Therapeutic agents such as teneligliptin, which have demonstrated potential for reducing inflammation and improving cardiac function in diabetic conditions[1], is a promising avenue for future clinical applications. These findings offer a valuable framework for the development of new treatments that address both glycemic control and the underlying inflammatory mechanisms contributing to DCM[6,9].
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