Date of Award
Master of Science (MS)
Phosphatases., Glucose--Metabolism., Lipids--Metabolism., Metabolism--Disorders--Animal models.
The function of MKP-2 in metabolism and metabolic diseases remains largely unknown. In obese conditions mitogen-activated protein kinase (MAPK) pathway get dysfunctional and MAP kinase phosphatases (MKPs) play major roles in regulating the activities of MAPKs. We examined the regulation of MKP-2 expression in vivo, under physiological and pathological conditions, in the liver and other insulin responsive tissues using diet-induced obesity models using novel MKP-2 knockout mice. Also, we examined MKP-2 expression in vitro using insulin sensitive cell lines. We found that MKP-2 is expressed in insulin-sensitive tissues/cells and overexpression may delay muscle cell differentiation. Our novel data demonstrate that under high fat-diet feeding conditions MKP-2 knockout mice are insulin sensitive and resistant to diet-induced obesity compared to MKP-2 wild type mice. We demonstrate that, in obese conditions, MKP-2 is overexpressed in the liver resulting in inactivation of MAPKs and thereby promoting development of obesity, fatty liver and metabolic dysfunction.
Fernando, Yanthrawaduge Savanie Sulakshana Devsirini, "Role of MKP-2 in glucose metabolism and stress-induced insulin resistance" (2021). Theses. 362.