Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

Background: Diabetic cardiomyopathy (DCM), which is a complication of diabetes, poses a great threat to public health. Recent studies have confirmed the role of NLRP3 (NOD-like Receptor protein 3) activation in DCM development through the inflammatory response. Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes. Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.

Aim: To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.

Methods: Streptozotocin was administered to induce diabetes in mice, followed by treatment with 30 mg/kg teneligliptin.

Results: Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening, ejection fraction, and heart rate; increases in creatine kinase-MB (CK-MB), aspartate transaminase (AST), and Lactate Dehydrogenase (LDH) levels; and upregulated NADPH Oxidase 4 were observed in diabetic mice, all of which were significantly reversed by teneligliptin. Moreover, NLRP3 inflammasome activation and increased release of interleukin-1β in diabetic mice were inhibited by teneligliptin. Primary mouse cardiomyocytes were treated with high glucose (30 mmol/L) with or without teneligliptin (2.5 or 5 µM) for 24 h. NLRP3 inflammasome activation. Increases in CK-MB, AST, and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin, and AMP (p-adenosine 5'-monophosphate)-p-AMPK (activated protein kinase) levels were increased. Furthermore, the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.

Conclusion: Overall, teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

AMPK; Diabetic cardiomyopathy; Interleukin-1β; NLRP3; Teneligliptin.