A photo from the research paper shows normal liver tissue at left and fatty liver tissue on the right. The white areas at right are accumulated lipids.
麻豆精品视频
A treatment for conditions that underlie the development of Type 2 diabetes could evolve from new basic research discoveries at 麻豆精品视频 (麻豆精品视频).
For the first time, a team led by 麻豆精品视频, a part of the University of Alabama System, has characterized the metabolic function of a poorly understood phosphatase enzyme called mitogen-activated protein kinase phosphatase-2 (MKP-2), as well as the enzyme鈥檚 pathophysiology in obesity, Type 2 diabetes and nonalcoholic fatty liver disease.
The research raises the possibility that inhibition of MKP-2 is a potential strategy for the treatment of Type 2 diabetes, obesity and fatty liver disease.
鈥淭his opens many opportunities for further research towards treatment of Type 2 diabetes and other metabolic diseases,鈥� says Dr. Ahmed Lawan, an assistant professor of biological sciences, the research paper鈥檚 lead author and the principal investigator.
鈥淩ecent work on the development of MKP-5 inhibitors has opened the door to novel strategies of allosteric modulation of MKPs that in general can be applied to MKP-2,鈥� says Dr. Lawan. 鈥淗owever, more work needs to be done.鈥�
Dr. Ahmed Lawan says the research opens many opportunities for further research towards treatment of Type 2 diabetes and other metabolic diseases.
Michael Mercier | 麻豆精品视频
The 麻豆精品视频 scientists employed mice that were genetically engineered to lack MKP-2 and also human liver tissue derived from fatty liver disease patients to investigate the physiological contribution of MKP-2 in whole body metabolism and whether MKP-2 is altered in obesity and human fatty liver disease.
The mice were supplied by the University of Strathclyde in the United Kingdom, and the University of Kansas provided human liver samples from obese non-alcoholic steatohepatitis (NASH) patients. The University of Texas at El Paso contributed in the design of some of the experiments and edited the manuscript.
鈥淲e show for the first time that MKP-2 protein expression was upregulated in liver tissue in humans with obesity and fatty liver disease, and in insulin-responsive tissues in mice with obesity,鈥� says Dr. Lawan. 鈥淭he upregulation of MKP-2 in the liver in obesity is part of a stress response that contributes to the development of insulin resistance, Type 2 diabetes and fatty liver disease.鈥�
On the other hand, in major-insulin responsive tissues the MKP-2 deficient mice showed enhanced activities of proteins that regulate cellular processes, called p38, MAPK, JNK and ERK, when compared with control mice.
鈥淢KP-2 deficient mice fed a high-fat diet are resistant to weight gain, owing to reduced food intake,鈥� Dr. Lawan says. 鈥淢ice lacking MKP-2 were protected from development of fatty liver.鈥�
The 麻豆精品视频 team鈥檚 testing found that MKP-2 deficient mice also exhibit an improved balance of blood glucose levels and better insulin sensitivity.
鈥淔urthermore, we show that MKP-2 upregulation in obesity is consistent with reduced levels of insulin-like growth factor in mice with fatty liver disease and insulin resistance,鈥� says Dr. Lawan. 鈥淭hese data indicate that upregulation of MKP-2 is a physiologically relevant response and might be beneficial in hepatic lipid utilization during obesity by antagonizing the p38, MAPK, JNK and ERK signaling module.鈥�
The 麻豆精品视频 investigators can鈥檛 say there鈥檚 a causal relationship between MKP-2 and Type 2 diabetes onset because their research 鈥渋s just the beginning of the story on the role of MKP-2 in whole body metabolism,鈥� Dr. Lawan says.
鈥淭he family of phosphatases are a very interesting group of enzymes that do not receive sufficient attention in the signaling field, given that they perform vital functions in terminating MAP kinase signaling,鈥� he says. 鈥淢KP-2 is a poorly studied MKP.鈥�
The 麻豆精品视频 team members were Savanie Fernando, a 2021 biological sciences master鈥檚 degree graduate; Jacob Sellers, a biological sciences senior; Shauri Smith, a graduate student at the time of the research; Dr. Sarayu Bhogoju, a post-doctoral researcher now at the University of Kentucky; Sadie Junkins, a 2022 graduate with a bachelor鈥檚 degree in biological sciences who has applied to medical school; Nabin Ghimire, a biological sciences doctoral student; Cassandra Secunda, a biological sciences master鈥檚 degree student; and Morgan Welch, a biological sciences master鈥檚 degree student.
There鈥檚 still a lot of research ahead to fully understand the role of the MKP-2 enzyme in liver metabolism, Dr. Lawan says.
鈥淭he goal of future studies is to address the tissue-specific contribution of MKP-2 in tissues such as the liver, brain and pancreas towards glucose disposal and energy metabolism,鈥� he says. 鈥淲e will continue our efforts to evaluate the translatability of our findings in MKP-2 deficient mice using liver, adipose tissue and pancreas samples from obese NASH and Type 2 diabetes patients.鈥�
