scholarly journals Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1617
Author(s):  
Pierluigi Scalia ◽  
Antonio Giordano ◽  
Caroline Martini ◽  
Stephen J. Williams
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Growth Factor ◽  
Solid Tumors ◽  
Common Finding ◽  
Absolute Increase ◽  
Preferential Expression ◽  
Exon 11

Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors.

scholarly journals Potential Role of Insulin Growth-Factor-Binding Protein 2 as Therapeutic Target for Obesity-Related Insulin Resistance

2021 ◽  
Vol 22 (3) ◽  
pp. 1133
Author(s):  
Hatim Boughanem ◽  
Elena M. Yubero-Serrano ◽  
José López-Miranda ◽  
Francisco J. Tinahones ◽  
Manuel Macias-Gonzalez
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Growth Factor ◽  
Therapeutic Target ◽  
Binding Protein ◽  
Factor Binding ◽  
Insulin Growth Factor

Evidence from observational and in vitro studies suggests that insulin growth-factor-binding protein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased. However, the physiological pathways have not been explored yet, and the relevance of IGFBP2 as an important pathway integrator of metabolic disorders is still unknown. Here, we review and discuss the molecular structure of IGFBP2 as the first element of regulating the expression of IGFBP2. We highlight an update of the association between low serum IGFBP2 and an increased risk of obesity, type 2 diabetes, metabolic syndrome, and low insulin sensitivity. We hypothesize mechanisms of IGFBP2 on the development of obesity and insulin resistance in an insulin-independent manner, which meant that could be evaluated as a therapeutic target. Finally, we cover the most interesting lifestyle modifications that regulate IGFBP2, since lifestyle factors (diet and/or physical activity) are associated with important variations in serum IGFBP2.

1758-P: Type 2 Diabetes–Associated Mood Disorders: Role of Insulin Resistance in Serotonergic Neurons

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1758-P
Author(s):  
HUGO MARTIN ◽  
SÉBASTIEN BULLICH ◽  
FABIEN DUCROCQ ◽  
MARION GRALAND ◽  
CLARA OLIVRY ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mood Disorders ◽  
Serotonergic Neurons ◽  
P Type

The role of vitamin D in the development of type 2 diabetes

2021 ◽  
Vol 19 (1) ◽  
pp. 44-52
Author(s):  
A.P. Shumilov ◽  
◽  
M.Yu. Semchenkova ◽  
D.S. Mikhalik ◽  
T.G. Avdeeva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Inverse Relationship ◽  
Biological Mechanisms ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Vitamin D Levels

Vitamin D plays an important role in decreasing the risk of developing type 2 diabetes by influencing calcium metabolism, thereby reducing β-cell dysfunction and preventing insulin resistance. The findings of research works are contradictory enough, although some of them demonstrated an inverse relationship between vitamin D levels and the incidence of type 2 diabetes. The article describes the biological mechanisms of relationships between vitamin D levels and type 2 diabetes, reviews the results of the studies conducted and summarizes the available data. Key words: vitamin D, type 2 diabetes mellitus, insulin resistance

scholarly journals Predictors of Insulin Resistance in Obesity and Type 2 Diabetes Mellitus - The Role of Magnesium

2017 ◽  
Vol 06 (04) ◽  
Author(s):  
Soetkin Milbouw ◽  
Julie Verhaegen ◽  
An Verrijken ◽  
Benedicte Y De Winter ◽  
Luc F Van Gaal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus

Abstract 18289: New Roles of the Interplay Between Endothelin and Insulin-like Growth Factor 1 in the Regulation of Vascular Redox State in Patients With Type 2 Diabetes and Coronary Atherosclerosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ioannis Akoumianakis ◽  
Marios Margaritis ◽  
Fabio Sanna ◽  
Laura Herdman ◽  
Constantinos Psarros ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Growth Factor ◽  
Nadph Oxidase ◽  
Redox State ◽  
Vascular Complications ◽  
Positive Association ◽  
Elevated Plasma ◽  
Enos Uncoupling

Background: Insulin resistance (IR) is associated with increased cardiovascular risk. Given that plasma endothelin (ET) is elevated in IR, we explored whether the variations in ET levels mediate the vascular complications of type 2 diabetes (T2DM), by exploring its links with vascular redox state in human vessels. Methods: The study population consisted of 383 patients undergoing coronary bypass surgery (CABG), 30% with T2DM. Levels of ET, insulin growth factor 1 (IGF1), insulin and glucose (to calculate HOMA-IR as an index of insulin resistance) were measured in plasma, while vascular superoxide (O2) was measured in saphenous vein segments obtained during surgery. Results: Patients with untreated T2DM had elevated plasma ET, contrary to treated patients with T2DM (A). A positive association was observed between plasma endothelin and IGF1 levels in non-T2DM, which was reversed in T2DM (B). Elevated plasma ET was associated with increased NADPH-stimulated O2- (indicative of higher NADPH oxidase activity) and more LNAME inhibitable O2- (suggestive of more eNOS uncoupling) in human vessels (C, D). Conclusions: We demonstrate that circulating ET is elevated in untreated T2DM but its levels are normalised after intensive glycaemic control. We also document a striking effect of DM on the balance between ET and IGF1, and we demonstrate for the first time in humans, that elevated plasma ET is associated with increased O2- generation in the vascular wall through activation of NADPH-oxidase and uncoupling of eNOS. This study shows that ET and its interplay with IGF1 is possibly a key mechanism linking T2DM with its vascular complications in humans

scholarly journals The effect of mid-life insulin resistance and type 2 diabetes on older-age cognitive state: the explanatory role of early-life advantage

Diabetologia ◽  
2019 ◽  
Vol 62 (10) ◽  
pp. 1891-1900
Author(s):  
Sarah-Naomi James ◽  
Andrew Wong ◽  
Therese Tillin ◽  
Rebecca Hardy ◽  
Nishi Chaturvedi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Early Life ◽  
Older Age ◽  
Cognitive State ◽  
Explanatory Role

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

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