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Autophagy and GLUT4: The missing pieces

Elhassan SAM, Candasamy M, Chan EWL, Bhattamisra SK

Diabetes Metab Syndr, 2018 Nov;12(6):1109-1116.
PMID: 29843994 DOI: 10.1016/j.dsx.2018.05.020

BACKGROUND: Autophagy is a process devoted to degrade and recycle cellular components inside mammalian cells through lysosomal system. It plays a main function in the pathophysiology of several diseases. In type 2 diabetes, works demonstrated the dual functions of autophagy in diabetes biology. Studies had approved the role of autophagy in promoting different routes for movement of integral membrane proteins to the plasma membrane. But its role in regulation of GLUT4 trafficking has not been widely observed. In normal conditions, insulin promotes GLUT4 translocation from intracellular membrane compartments to the plasma membrane, while in type 2 diabetes defects occur in this translocation.
METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.
RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.
CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.
Effect of madecassoside and catalpol in amelioration of insulin sensitivity in pancreatic (INS-1E) β-cell line

Elhassan SAM, Candasamy M, Ching TS, Heng YK, Bhattamisra SK

Nat Prod Res, 2021 Nov;35(22):4627-4631.
PMID: 31797687 DOI: 10.1080/14786419.2019.1696794

Currently, type 2 diabetes mellitus (T2D) has emerged as global burden disease. Herbal drugs with antidiabetic activities are attracting the attention. Madecassoside and catalpol are herbal compounds having strong antioxidant and glucose lowering activity. Madecassoside and catalpol were investigated for their effect on insulin sensitivity using pancreatic INS-1E cells. Cytotoxicity of these compounds was evaluated by MTT assay. Glucose-stimulated insulin secretion (GSIS) and expression of insulin signalling proteins were studied in presence of madecassoside and catalpol. Results revealed that madecassoside and catalpol enhanced the GSIS without cytotoxic effect. Madecassoside (30 µM) and catalpol (40 µM) increased the insulin secretion in response to high glucose (16.7 mM) stimulation. Subsequently, madecassoside and catalpol showed elevated expression of p-IRS-1, Akt, and p-Akt proteins. Madecassoside and catalpol after 24 h of incubation in pancreatic INS-1E cells with high glucose concentration (30 mM) ameliorated the insulin secretion.
Fulltext The roles of circular RNAs in human development and diseases

Lee ECS, Elhassan SAM, Lim GPL, Kok WH, Tan SW, Leong EN, et al.

Biomed Pharmacother, 2019 Mar;111:198-208.
PMID: 30583227 DOI: 10.1016/j.biopha.2018.12.052

For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.

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