scholarly journals The Role of Insulin Receptor Isoforms in Diabetes and Its Metabolic and Vascular Complications

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
O. Escribano ◽  
N. Beneit ◽  
C. Rubio-Longás ◽  
A. R. López-Pastor ◽  
A. Gómez-Hernández
Keyword(s):  
Insulin Receptor ◽  
Vascular Complications ◽  
Cell Types ◽  
Metabolic Effects ◽  
Future Research ◽  
Receptor Isoforms ◽  
Insulin Receptor Isoforms ◽  
Treatment Of Diabetes ◽  
Different Cell Types

The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and IRB. The differential physiological and pathological role of both isoforms is not completely known, and it is determinant the different binding affinity for insulin-like growth factor. IRB is more abundant in adult tissues and it exerts mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal and prenatal period and exerts mitogenic actions. However, the change in the expression profile of both IR isoforms and its dysregulation are associated with the development of different pathologies, such as cancer, insulin resistance, diabetes, obesity, and atherosclerosis. In some of them, there is a significant increase of IRA/IRB ratio conferring a proliferative and migratory advantage to different cell types and favouring IGF-II actions with a sustained detriment in the metabolic effects of insulin. This review discussed specifically the role of IR isoforms as well as IGF-IR in diabetes and its associated complications as obesity and atherosclerosis. Future research with new IR modulators might be considered as possible targets to improve the treatment of diabetes and its associated complications.

scholarly journals Potential role of insulin receptor isoforms and IGF receptors in plaque instability of human and experimental atherosclerosis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Nuria Beneit ◽  
José Luis Martín-Ventura ◽  
Carlota Rubio-Longás ◽  
Óscar Escribano ◽  
Gema García-Gómez ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Potential Role ◽  
Experimental Atherosclerosis ◽  
Plaque Instability ◽  
Receptor Isoforms ◽  
Igf Receptors ◽  
Insulin Receptor Isoforms

406. Regulation of insulin receptor and its substrates by follicle stimulating hormone in granulosa cells

2008 ◽  
Vol 20 (9) ◽  
pp. 86
Author(s):  
J. Taneja ◽  
R. Singh
Keyword(s):  
Insulin Receptor ◽  
Granulosa Cells ◽  
Glycogen Synthesis ◽  
Follicular Development ◽  
Serine Phosphorylation ◽  
Dependent Manner ◽  
Receptor Isoforms ◽  
Insulin Receptor Signalling ◽  
Insulin Receptor Isoforms

Insulin receptor signalling receptor regulates the process of follicular development and maturation, however the regulation of insulin receptor (IR) and its signalling component during folliculogenesis is not well understood. This study demonstrates FSH mediated regulation of insulin receptor isoforms specially IR-B, its substrates and some of the insulin related responses like glycogen synthesis and cell proliferation. There was significant increase in mRNAs expression for insulin receptor (IR) isoforms, IR-A and IR-B in ovary in response to PMSG and in granulosa cells (GCs) in response to FSH. IR protein increased in GCs in response to FSH in a dose and time dependent manner. Interestingly, the expression of mRNAs and proteins for IRS-1 and IRS-2 increased significantly in GCs by FSH. Serine phosphorylation (Ser 636/639) of IRS-1 was decreased by FSH, thus facilitating IRS-1 activation. FSH stimulated glycogen synthesis in a dose dependent manner both by PI 3 kinase dependent and independent pathways. Insulin regulated the amount of FSH stimulated glycogen synthesis by granulosa cells. In contrast, FSH and insulin synergistically stimulated glycogen synthesis GC proliferation which was completely inhibited by LY294002. Knockdown of IRS-1 mRNA by siRNA inhibited FSH stimulated GC proliferation indicating an important role of IRS-1 downstream of FSH. Further research is required to delineate the signalling components involving IRS-1 and IRS-2 in response to FSH and thus involved in the cross-talk between FSH and insulin in GCs. Results thus demonstrate that pituitary FSH regulates insulin receptor and its substrates in rat GCs which might be important for follicular growth and oocyte development.

scholarly journals Fostering “Education”: Do Extracellular Vesicles Exploit Their Own Delivery Code?

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1741
Author(s):  
Mayra Paolillo ◽  
Sergio Comincini ◽  
Sergio Schinelli
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Surface Membrane ◽  
Cell Types ◽  
Future Research ◽  
Target Cells ◽  
Bioinformatic Tools ◽  
Experimental Approaches ◽  
Different Cell Types

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

scholarly journals The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1065
Author(s):  
Armando Rubio-Ramos ◽  
Leticia Labat-de-Hoz ◽  
Isabel Correas ◽  
Miguel A. Alonso
Keyword(s):  
Epithelial Cells ◽  
Large Body ◽  
Original Description ◽  
Cell Types ◽  
Future Research ◽  
Transmembrane Segments ◽  
Epsilon Toxin ◽  
Proteolipid Proteins ◽  
Polarized Epithelial Cells

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

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