Liraglutide (Chongqing Paijin)

Diabetes mellitus (DM) is a growing metabolic disease worldwide, associated with severe complications. Glucagon-like peptide-1 analogs and sodium-glucose cotransporter-2 inhibitors are promising therapeutic options for diabetic cardiomyopathy (DCM), although their cardioprotective mechanisms are not yet fully understood.

This study evaluates the effects of liraglutide and empagliflozin on oxidative stress, inflammation, and histological changes in cardiac tissue in DCM.

Thirty-seven male Wistar albino rats were divided into four groups. Diabetes was induced in three groups using streptozotocin and nicotinamide. The groups were: (1) Control, (2) DM, (3) DM + Liraglutide (0.6 mg/kg, subcutaneously, 8 weeks), and (4) DM + Empagliflozin (30 mg/kg, oral gavage, 8 weeks). Blood samples were analyzed through enzyme-linked immunosorbent assay for tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), malondialdehyde (MDA), superoxide dismutase (SOD), advanced glycation end (AGEs) products, and insulin. Cardiac tissue was examined histopathologically.

Diabetes significantly increased blood glucose, IL-1, TNF-α, MDA, and AGEs (p < 0.01), while SOD levels decreased (p < 0.01), alongside myocardial damage. Liraglutide and empagliflozin improved all parameters (p < 0.01).

Liraglutide and empagliflozin mitigate diabetes-induced cardiac damage, likely by reducing fibrosis, oxidative stress, and inflammation.

The pancreatic islet, historically described as a binary system of insulin-secreting beta cells and glucagon-secreting alpha cells, is increasingly recognized as a complex paracrine network contributing to glucose homeostasis. Alpha-to-beta cell communication is not merely modulatory but a decisive mechanism sustaining islet function under metabolic stress. Alpha cell distribution, structural specializations at the alpha-beta interface, and adaptations in signaling pathways collectively shape glycemic set points and beta cell resilience. Recent studies highlight the context-dependent nature of this intra-islet crosstalk. Visa et al. demonstrated that prediabetic stress in Western diet-fed mice remodels islet cytoarchitecture in a sex-dependent manner, enhancing alpha-to-beta signaling and Ca²⁺ dynamics, and thereby preserving insulin secretion more effectively in females than in males. Experiments using a glucagon receptor antagonist in human islets confirmed that glucagon paracrine signaling is essential for this adaptive enhancement, particularly the increased Ca²⁺ dynamics in female islets under high metabolic demand. Mechanistic studies further revealed that the GLP-1 receptor forms specialized nanodomains at the alpha-beta junction that undergo pre-internalization, priming beta cells for rapid Ca²⁺ influx and heightened metabolic responsiveness. Collectively, these findings highlight intra-islet communication as a critical determinant of adaptation or failure in diabetes progression. However, conflicting evidence from beta cell-only islets, which display enhanced glucose-stimulated insulin secretion, together with reports that long-term exposure to the GLP-1 analog liraglutide can compromise beta cell function, presents a paradox that challenges current models of intra-islet regulation. Understanding these nuances is crucial for translating intra-islet signaling into targeted therapeutic strategies and regenerative tissue engineering.