ABSTRACT: Despite recent advancements in clinical drugs, diabetes treatment still needs further progress. As such, ongoing research has attempted to determine the precise molecular mechanisms of the disorder. Specifically, evidence supports that several signaling pathways play pivotal roles in the development of diabetes. However, the exact molecular mechanisms of diabetes still need to be explored. This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-? signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. Dysregulated autophagy in pancreatic ? cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. Another pathway, TGF-? signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. Subsequently, drugs that target TGF-? signaling, especially naturally derived ones such as resveratrol, puerarin, curcumin, hesperidin, and silymarin, as well as Propolis, Lycopus lucidus, and Momordica charantia extracts, may become promising alternatives to current drugs in diabetes treatment. This review provides keen insights into novel therapeutic strategies for the medical care of diabetes.
