Abstract
Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The Hippo signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy-basic research. MST1 and LATS2, as major upstream signaling kinases of the Hippo pathway, are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the Hippo pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and completely characterize the role of this pathway in diabetes. Therapy consisting of slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment in the future.
Highlights
Diabetes mellitus is a heterogeneous disorder with multiple etiologies [1,2]
The arrest of the mechanistic target of rapamycin 1 (mTORC1) pathway was revealed by the blocking of β cell apoptosis, which clearly showed that the pro-apoptotic effect of large tumor suppressor 2 (LATS2) is mTORC1-dependent and is over-activated by LATS2 in diabetes in INS-1E cells and human pancreatic islets [13]
The results of basic research on the effects obtained from modulation of Hippo pathway signaling allow the design of a breakthrough therapy that addresses all the shortcomings of the current treatment regimen
Summary
Diabetes mellitus is a heterogeneous disorder with multiple etiologies [1,2]. The most prevalent in adults is type 2, a chronic metabolic illness with increasing medical and financial costs [3,4]. Primary studies have shown that the abnormal expression of the Hippo signaling pathway in tested peripheral tissues may initiate type 2 diabetes and be associated with the gut microbiota, as well as with the aging process [51]. The identification of those signaling pathways on which the functioning and survival of pancreatic β cells depends is a prerequisite for a full understanding of the mechanisms related to dysfunction and will be the basis for introducing new solutions in therapy [43]. The aim of this review is to delineate the role of the Hippo signaling pathway in pancreatic β cell apoptosis in diabetes, and the possibilities it presents in eliminating the consequences of diabetes in both cellular and systemic terms
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