Pancreas · 2016
Combination of Telmisartan and Linagliptin Preserves Pancreatic Islet Cell Function and Morphology in db/db Mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhao Shuiling, Chan Leo Ka Yu, Chen Lihua, Cheng Tsz Wai, Klein Thomas, Leung Po Sing
Аннотация
OBJECTIVES: The present study aimed to investigate the synergistic action of telmisartan and linagliptin in ameliorating pancreatic islet functions and morphology in type 2 diabetes mellitus and to delineate the molecular signaling pathway involved.
METHODS: db/db mice were given telmisartan (3 mg/kg) or linagliptin (3 mg/kg) alone or in combination, daily for 8 weeks, and were studied in vivo by fasting and random blood glucose tests, oral glucose tolerance tests, and intraperitoneal insulin tolerance tests, as well as ex vivo by glucose-stimulated insulin secretion and morphology of pancreatic islets. The underlying signaling pathways were examined by Western blot, real-time quantitative polymerase chain reaction, and dihydroethidium staining analyses using mouse pancreatic islets and rat β-insulinoma cells.
RESULTS: Telmisartan/linagliptin combination induced significantly better glucose homeostasis than the monotherapies. Posttreatment reactive oxygen species level was suppressed most significantly after the telmisartan/linagliptin combined therapy, whereas no significant change in peroxisome proliferator-activated receptor γ expressions was observed after treatments.
CONCLUSIONS: The telmisartan/linagliptin combination preserved pancreatic islet cell functions and morphology via reduction of oxidative stress but independent of the peroxisome proliferator-activated receptor γ pathway. Our data shed light on the therapeutic potential of using the telmisartan/linagliptin combination in the treatment of human type 2 diabetes mellitus and its related complications.
METHODS: db/db mice were given telmisartan (3 mg/kg) or linagliptin (3 mg/kg) alone or in combination, daily for 8 weeks, and were studied in vivo by fasting and random blood glucose tests, oral glucose tolerance tests, and intraperitoneal insulin tolerance tests, as well as ex vivo by glucose-stimulated insulin secretion and morphology of pancreatic islets. The underlying signaling pathways were examined by Western blot, real-time quantitative polymerase chain reaction, and dihydroethidium staining analyses using mouse pancreatic islets and rat β-insulinoma cells.
RESULTS: Telmisartan/linagliptin combination induced significantly better glucose homeostasis than the monotherapies. Posttreatment reactive oxygen species level was suppressed most significantly after the telmisartan/linagliptin combined therapy, whereas no significant change in peroxisome proliferator-activated receptor γ expressions was observed after treatments.
CONCLUSIONS: The telmisartan/linagliptin combination preserved pancreatic islet cell functions and morphology via reduction of oxidative stress but independent of the peroxisome proliferator-activated receptor γ pathway. Our data shed light on the therapeutic potential of using the telmisartan/linagliptin combination in the treatment of human type 2 diabetes mellitus and its related complications.
Предметные рубрики MeSH
Angiotensin II Type 1 Receptor BlockersAnimalsBenzimidazolesBenzoatesBlotting, WesternCell Line, TumorDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDisease Models, AnimalDrug Therapy, CombinationFemaleGlucose Tolerance TestHumansImmunohistochemistryIslets of LangerhansLinagliptinMiceMice, Inbred C57BLOxidative StressPPAR gammaPancreasReactive Oxygen SpeciesTelmisartan