SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

Wang, Dao‐Cai; Yan, Tingting; Cui, Bin; Liu, Feng; Liu, Xiaopeng; Xie, Yongmei

doi:10.1111/fcp.12611

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Therefore, exploration of Smad3-targeted expression modification or chemical inhibitors may be promising approaches for the treatment of T2DM. Recently, it is reported that administration of SIS3, a specific inhibitor of Smad3, in HFD-fed mice reduces body weight and hyperglycemia with improved glucose intolerance and insulin resistance [115]. Our unpublished data also suggests a protective role of SIS3 against diabetic phenotype with improved β cell survival in db/db mice.…”

Section: Conclusion Perspectives and Future Directionssupporting

confidence: 65%

Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes

Wang

Zhao

et al. 2022

Biomolecules

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Beta (β) cell dysfunction or loss is the common pathological feature in all types of diabetes mellitus (diabetes). Resolving the underlying mechanism may facilitate the treatment of diabetes by preserving the β cell population and function. It is known that TGF-β signaling plays diverse roles in β cell development, function, proliferation, apoptosis, and dedifferentiation. Inhibition of TGF-β signaling expands β cell lineage in the development. However, deletion of Tgfbr1 has no influence on insulin demand-induced but abolishes inflammation-induced β cell proliferation. Among canonical TGF-β signaling, Smad3 but not Smad2 is the predominant repressor of β cell proliferation in response to systemic insulin demand. Deletion of Smad3 simultaneously improves β cell function, apoptosis, and systemic insulin resistance with the consequence of eliminated overt diabetes in diabetic mouse models, revealing Smad3 as a key mediator and ideal therapeutic target for type-2 diabetes. However, Smad7 shows controversial effects on β cell proliferation and glucose homeostasis in animal studies. On the other hand, overexpression of Tgfb1 prevents β cells from autoimmune destruction without influence on β cell function. All these findings reveal the diverse regulatory roles of TGF-β signaling in β cell biology.

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Section: Conclusion Perspectives and Future Directionssupporting

confidence: 65%

Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes

Wang

Zhao

et al. 2022

Biomolecules

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Design, Synthesis, and Biological Evaluation of Novel Pyrrolo [2,3-b] Pyridine Derivatives for Nonalcoholic Fatty Liver Disease

Yao

et al. 2022

Journal of Chemistry

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Nonalcoholic fatty liver disease (NAFLD) is featured with liver fat infiltration and accumulation with no connection with overdrinking. With the rising trends and no FDA-approved drugs, NAFLD attracts global attention. In this study, we successfully synthesized 18 novel SIS3 derivatives and evaluated them for pharmacological activity. F-9 and F-15 had potent weight-losing effects. Importantly, intraperitoneal administration of F-9 at 10 mg·kg−1·day−1 for 5 weeks had the most excellent effects to reduce the weight of the body, liver, and fat, as well as adjusting serum levels of AST, ALT, TC, TG, HDL, and LDL. H&E staining showed that F-9 could suppress fat deposition and increase the adipocyte size in the liver.

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SIS3, a good candidate for the reverse of type 2 diabetes mellitus in mice

Cited by 2 publications

References 29 publications

Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes

Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes

Design, Synthesis, and Biological Evaluation of Novel Pyrrolo [2,3-b] Pyridine Derivatives for Nonalcoholic Fatty Liver Disease

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