Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation. It is noteworthy that TFEB activation is context-dependent; therefore, its regulation is subjected to coordinated mechanisms that respond not only to nutrient fluctuations but also to stress cell programs to ensure proper cell homeostasis and organismal health. In this review, we provide updated insights into novel post-translational modifications that regulate TFEB activity and give an overview of TFEB beyond its widely known role in autophagy and the lysosomal pathway, thus opening the possibility of considering TFEB as a potential therapeutic target.

Glucotoxicity may exert its deleterious effects on pancreatic β-cell function via a myriad of mechanisms, leading to impaired insulin secretion and, eventually, type 2 diabetes. β-cell communication requires gap junction channels to be present among these cells. Gap junctions are constituted by transmembrane proteins of the connexins (Cxs) family. Two Cx genes have been identified in β cells, Cx36 and Cx30.2. We have found evidence that the glucose concentration on its own is sufficient to regulate Cx30.2 gene expression in mouse islets. In this work, we examine the involvement of the Cx30.2 protein in the survival of β cells (RIN-m5F). Methods: RIN-m5F cells were cultured in 5 mM D-glucose (normal) or 30 mM D-glucose (high glucose) for 24 h. Cx30.2 siRNAs was used to downregulate Cx30.2 expression. Apoptosis was measured by means of TUNEL, an annexin V staining method, and the cleaved form of the caspase-3 protein was determined using Western blot. Results: High glucose did not induce apoptosis in RIN-m5F β cells after 24 h; interestingly, high glucose increased the Cx30.2 total protein levels. Moreover, this work found that the downregulation of Cx30.2 expression in high glucose promoted apoptosis in RIN-m5F cells. Conclusion: The data suggest that the upregulation of Cx30.2 protects β cells from hyperglycemia-induced apoptosis. Furthermore, Cx30.2 may be a promising avenue of therapeutic investigation for the treatment of glucose metabolic disorders.

Autophagy is a crucial mechanism for the functioning and survival of pancreatic beta cells. Its dysregulation has been associated with obesity, insulin resistance, and glucose intolerance. Furthermore, decreased autophagy in insulin-secret ing beta cells has been reported to contribute to the devel opment of type 2 diabetes mellitus (T2DM), which constitutes about 95% of all diabetes cases and is a chronic metabolic disease that it currently affects millions of people around the world. In different models of rodents, whether diabetic or obese, it has been observed that treatment with autophagy enhancers lowers glucose levels, increases insulin sensitivity, and protects beta cells from apoptosis. As stated above, it has recently been proposed to carry out an early intervention in patients with T2DM, using drugs that promote autophagy, which could help preserve the mass of beta cells and prevent the progression of the disease. This review provides an over view of the importance of the physiological process of auto phagy and its imminent role in the development of T2DM. Keywords: Pancreatic beta cells; autophagy; cell death; diabetes mellitus type 2

México presenta una alta prevalencia de enfermedades crónico-metabólicas, destacando de entre estas la diabetes mellitus tipo 2 (DMT2). Es esencial profundizar en la asociación entre la covid-19 y la DMT2, dado que ambas enfermedades tienen efectos bidireccionales. La diabetes puede incrementar la patogenicidad del virus SARS-CoV-2, debido a las alteraciones metabólicas que subyacen a esta enfermedad, lo que resulta en un aumento de la susceptibilidad y la severidad de la covid-19 entre los pacientes diabéticos, siendo una población de alto riesgo de mortalidad. Por otra parte, la infección por SARS-CoV-2 puede predisponer a los individuos a hiperglucemia o diabetes de nueva aparición. Con el propósito de comprender la asociación que existe entre la covid-19 y la DMT2, en esta revisión se enfatiza el tropismo del virus SARS-CoV-2 por las células beta pancreáticas secretoras de insulina, así como el efecto que tiene el virus sobre la fisiología de estas células.