BACKGROUND: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM. METHODS: T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups. RESULTS: Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ± 13.2 and 279.7 ± 17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ± 8.0 to 42.7 ± 3.2 mg/dL and from 229.7 ± 25.4 to 100.7 ± 17.1 mg/dL, in diabetic rats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ± 1.5 to 13.3 ± 2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabetic rats. CONCLUSION: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DM rats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future.
BACKGROUND: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM. METHODS:T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups. RESULTS:Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ± 13.2 and 279.7 ± 17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ± 8.0 to 42.7 ± 3.2 mg/dL and from 229.7 ± 25.4 to 100.7 ± 17.1 mg/dL, in diabeticrats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ± 1.5 to 13.3 ± 2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabeticrats. CONCLUSION: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DMrats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future.
Authors: Gizele Cabral Costa; Tadeu Lima Montagnoli; Jaqueline Soares Da Silva; Allan Kardec Nogueira de Alencar; Luis Eduardo Reina Gamba; Bryelle Eccard Oliveira Alves; Marina Moraes Carvalho da Silva; Margarete Manhães Trachez; José Hamilton M do Nascimento; Pedro Moreno Pimentel-Coelho; Rosália Mendez-Otero; Lidia Moreira Lima; Eliezer J Barreiro; Roberto Takashi Sudo; Gisele Zapata-Sudo Journal: Drug Des Devel Ther Date: 2020-08-17 Impact factor: 4.162
Authors: Rodrigo Daza-Arnedo; Jorge-Eduardo Rico-Fontalvo; Nehomar Pájaro-Galvis; Víctor Leal-Martínez; Emilio Abuabara-Franco; María Raad-Sarabia; Juan Montejo-Hernández; María Cardona-Blanco; José Cabrales-Juan; Isabella Uparella-Gulfo; Luis Salgado Montiel Journal: Kidney Med Date: 2021-09-29
Authors: Esraa M Zakaria; Walaa M Tawfeek; Mohamed H Hassanin; Mohammed Y Hassaballah Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2022-08-10 Impact factor: 3.195