Loss of low-molecular-weight protein tyrosine phosphatase shows limited improvement in glucose tolerance but causes mild cardiac hypertrophy in mice
| Autor: | Sharon, Jensen-Cody, Erin S, Coyne, Xunshan, Ding, Anu, Sebin, Jen, Vogel, Jaclyn, Goldstein, Thomas W, Rosahl, Heather H, Zhou, Hugues, Jacobs, Marie-France, Champy, Ghina Bou, About, Saswata, Talukdar, Yingjiang, Zhou |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 322:E517-E527 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Insulin resistance is a major public health burden that often results in other comorbidities including type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. An insulin sensitizer has the potential to become a disease-modifying therapy. It remains an unmet medical need to identify therapeutics that target the insulin signaling pathway to treat insulin resistance. Low-molecular-weight protein tyrosine phosphatase (LMPTP) negatively regulates insulin signaling and has emerged as a potential therapeutic target for insulin sensitization. Genetic studies have demonstrated that LMPTP is positively associated with obesity in humans and promotes insulin resistance in rodents. A recent study showed that pharmacological inhibition or genetic deletion of LMPTP protects mice from high-fat diet-induced insulin resistance and diabetes. Here, we show that loss of LMPTP by genetic deletion has no significant effects on improving glucose tolerance in lean or diet-induced obese mice. Furthermore, our data demonstrate that LMPTP deficiency potentiates cardiac hypertrophy that leads to mild cardiac dysfunction. Our findings suggest that the development of LMPTP inhibitors for the treatment of insulin resistance and type 2 diabetes should be reevaluated, and further studies are needed to characterize the molecular and pathophysiological role of LMPTP. |
| Databáze: | OpenAIRE |
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