scholarly journals Insulin signal transduction is impaired in the type 2 diabetic retina

2019 ◽  
Author(s):  
Youde Jiang ◽  
Li Liu ◽  
Hainan Li ◽  
Jie-Mei Wang ◽  
Jena J. Steinle
Keyword(s):  
Type 2 Diabetes ◽  
Signal Transduction ◽  
Insulin Receptor ◽  
Caspase 3 ◽  
Necrosis Factor Alpha ◽  
Akt Phosphorylation ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Diabetic Retina

AbstractRates of type 2 diabetes are reaching epidemic levels. Yet, the tissue specific alterations due to insulin resistance are only recently being investigated. The goal of the present study was to evaluate retinal insulin signal transduction in a common mouse model of type 2 diabetes, the db/db mouse. Retinal lysates from five month old male db/db and db/+ (control) mice were collected and processed for Western blotting or ELISA analyses for insulin receptor, insulin receptor substrate-1 (IRS-1), Akt, tumor necrosis factor alpha (TNFα) and caspase 3 levels. Data demonstrate increased TNFα and IRS-1 phosphorylation on serine 307. This led to decreased Akt phosphorylation on serine 473 and increased cleavage of caspase 3. Taken together, the data suggest dysfunctional insulin signaling in the retina of the db/db mouse.

scholarly journals Insulin Signal Transduction Perturbations in Insulin Resistance

2021 ◽  
Vol 22 (16) ◽  
pp. 8590
Author(s):  
Mariyam Khalid ◽  
Juma Alkaabi ◽  
Moien A. B. Khan ◽  
Abdu Adem
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Signal Transduction ◽  
Type 2 Diabetes Mellitus ◽  
Β Cell ◽  
High Blood Glucose ◽  
Insulin Signal Transduction ◽  
Insulin Signal

Type 2 diabetes mellitus is a widespread medical condition, characterized by high blood glucose and inadequate insulin action, which leads to insulin resistance. Insulin resistance in insulin-responsive tissues precedes the onset of pancreatic β-cell dysfunction. Multiple molecular and pathophysiological mechanisms are involved in insulin resistance. Insulin resistance is a consequence of a complex combination of metabolic disorders, lipotoxicity, glucotoxicity, and inflammation. There is ample evidence linking different mechanistic approaches as the cause of insulin resistance, but no central mechanism is yet described as an underlying reason behind this condition. This review combines and interlinks the defects in the insulin signal transduction pathway of the insulin resistance state with special emphasis on the AGE-RAGE-NF-κB axis. Here, we describe important factors that play a crucial role in the pathogenesis of insulin resistance to provide directionality for the events. The interplay of inflammation and oxidative stress that leads to β-cell decline through the IAPP-RAGE induced β-cell toxicity is also addressed. Overall, by generating a comprehensive overview of the plethora of mechanisms involved in insulin resistance, we focus on the establishment of unifying mechanisms to provide new insights for the future interventions of type 2 diabetes mellitus.

scholarly journals MicroRNAs as Regulators of Insulin Signaling: Research Updates and Potential Therapeutic Perspectives in Type 2 Diabetes

2018 ◽  
Vol 19 (12) ◽  
pp. 3705 ◽  
Author(s):  
Laura Nigi ◽  
Giuseppina Grieco ◽  
Giuliana Ventriglia ◽  
Noemi Brusco ◽  
Francesca Mancarella ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Signal Transduction ◽  
Insulin Signaling ◽  
Messenger Rna ◽  
Specific Binding ◽  
Rna Molecules ◽  
Insulin Signal Transduction ◽  
Insulin Signal

The insulin signaling pathway is composed of a large number of molecules that positively or negatively modulate insulin specific signal transduction following its binding to the cognate receptor. Given the importance of the final effects of insulin signal transduction, it is conceivable that many regulators are needed in order to tightly control the metabolic or proliferative functional outputs. MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively modulate gene expression through their specific binding within the 3′UTR sequence of messenger RNA (mRNA), thus causing mRNA decoy or translational inhibition. In the last decade, miRNAs have been addressed as pivotal cellular rheostats which control many fundamental signaling pathways, including insulin signal transduction. Several studies demonstrated that multiple alterations of miRNAs expression or function are relevant for the development of insulin resistance in type 2 diabetes (T2D); such alterations have been highlighted in multiple insulin target organs including liver, muscles, and adipose tissue. Indirectly, miRNAs have been identified as modulators of inflammation-derived insulin resistance, by controlling/tuning the activity of innate immune cells in insulin target tissues. Here, we review main findings on miRNA functions as modulators of insulin signaling in physiologic- or in T2D insulin resistance- status. Additionally, we report the latest hypotheses of prospective therapies involving miRNAs as potential targets for future drugs in T2D.

scholarly journals Insulin Signal Transduction in Skeletal Muscle From Glucose-Intolerant Relatives With Type 2 Diabetes

Diabetes ◽  
2001 ◽  
Vol 50 (12) ◽  
pp. 2770-2778 ◽  
Author(s):  
H. Storgaard ◽  
X. M. Song ◽  
C. B. Jensen ◽  
S. Madsbad ◽  
M. Bjornholm ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Signal Transduction ◽  
Insulin Signal Transduction ◽  
Insulin Signal

scholarly journals Insulin Signal Transduction by a Mutant Human Insulin Receptor Lacking the NPEY Sequence

1997 ◽  
Vol 272 (36) ◽  
pp. 22884-22890 ◽  
Author(s):  
Paulos Berhanu ◽  
Celia Anderson ◽  
Matt Hickman ◽  
Theodore P. Ciaraldi
Keyword(s):  
Signal Transduction ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Insulin Signal Transduction ◽  
Insulin Signal ◽  
Human Insulin Receptor

scholarly journals The NAD(P)H Oxidase Homolog Nox4 Modulates Insulin-Stimulated Generation of H2O2 and Plays an Integral Role in Insulin Signal Transduction

2004 ◽  
Vol 24 (5) ◽  
pp. 1844-1854 ◽  
Author(s):  
Kalyankar Mahadev ◽  
Hiroyuki Motoshima ◽  
Xiangdong Wu ◽  
Jean Marie Ruddy ◽  
Rebecca S. Arnold ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Insulin Action ◽  
Protein Tyrosine Phosphatases ◽  
Cellular Protein ◽  
Dominant Negative ◽  
Target Cells ◽  
Insulin Signal Transduction ◽  
Insulin Signal

ABSTRACT Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action.

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