Insulin‐Mediated PI3K and AKT Signaling

Kwon, Hyokjoon; Pessin, Jeffrey E.

doi:10.1002/9781119436812.ch39

Cited by 4 publications

(4 citation statements)

References 86 publications

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“…First, an autophosphorylation event occurs on the intracellular tail of the IR, recruiting the insulin receptor substrates 1 and 2 (IRS1 and IRS2). Tyrosine phosphorylation of IRS1/2 leads to downstream activation of the kinases phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) ( Figure 1 ) [ 27 , 28 ]. This PI3K/Akt/mTOR signaling pathway impacts a wide variety of cellular functions, including synaptic plasticity, cholesterol synthesis, neuronal survival, and neurotransmitter trafficking [ [29] , [30] , [31] , [32] ].…”

Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

The brain as an insulin-sensitive metabolic organ

Milstein

Ferris

2021

Molecular Metabolism

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Background The brain was once thought of as an insulin-insensitive organ. We now know that the insulin receptor is present throughout the brain and serves important functions in whole-body metabolism and brain function. Brain insulin signaling is involved not only in brain homeostatic processes but also neuropathological processes such as cognitive decline and Alzheimer's disease. Scope of review In this review, we provide an overview of insulin signaling within the brain and the metabolic impact of brain insulin resistance and discuss Alzheimer's disease, one of the neurologic diseases most closely associated with brain insulin resistance. Major conclusions While brain insulin signaling plays only a small role in central nervous system glucose regulation, it has a significant impact on the brain's metabolic health. Normal insulin signaling is important for mitochondrial functioning and normal food intake. Brain insulin resistance contributes to obesity and may also play an important role in neurodegeneration.

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Section: Insulin Receptor Expression and Signaling In The Brainmentioning

confidence: 99%

The brain as an insulin-sensitive metabolic organ

Milstein

Ferris

2021

Molecular Metabolism

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“…The downregulation of ‘Insulin signaling’ pathway was consistent with AKT1 downregulation [ 149 ] and was intriguing. Indeed, the long-term effect of niacin treatment on the impairment of insulin sensitivity has been recently debated [ 98 , 150 ].…”

Section: Discussionmentioning

confidence: 78%

Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation

et al. 2023

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The objective of our study was to assess the effect of rumen-protected niacin supplementation on the transcriptome of liver tissue in growing Angus × Simmental steers and heifers through RNA-seq analysis. Consequently, we wanted to assess the known role of niacin in the physiological processes of vasodilation, detoxification, and immune function in beef hepatic tissue. Normal weaned calves (~8 months old) were provided either a control diet or a diet supplemented with rumen-protected niacin (6 g/hd/d) for a 30-day period, followed by a liver biopsy. We observed a significant list of changes at the transcriptome level due to rumen-protected niacin supplementation. Several metabolic pathways revealed potential positive effects to the animal’s liver metabolism due to administration of rumen-protected niacin; for example, a decrease in lipolysis, apoptosis, inflammatory responses, atherosclerosis, oxidative stress, fibrosis, and vasodilation-related pathways. Therefore, results from our study showed that the liver transcriptional machinery switched several metabolic pathways to a condition that could potentially benefit the health status of animals supplemented with rumen-protected niacin. In conclusion, based on the results of our study, we can suggest the utilization of rumen-protected niacin supplementation as a nutritional strategy could improve the health status of growing beef cattle in different beef production stages, such as backgrounding operations or new arrivals to a feedlot.

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“…This efflux inhibits FOXO1 activity, thereby downregulating PEPCK and inhibiting gluconeogenesis. In addition, some of the glucose from the circulation is taken up by the liver through GLUT2, followed by de novo lipogenesis under insulin stimulation [ 31 ]. The liver insulin signaling pathway most likely also occurs in the HepG2 cell line that displays the hepatocytic phenotype ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

In Vitro Insulin Resistance Model: A Recent Update

et al. 2023

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Insulin resistance, which affects insulin-sensitive tissues, including adipose tissues, skeletal muscle, and the liver, is the central pathophysiological mechanism underlying type 2 diabetes progression. Decreased glucose uptake in insulin-sensitive tissues disrupts insulin signaling pathways, particularly the PI3K/Akt pathway. An in vitro model is appropriate for studying the cellular and molecular mechanisms underlying insulin resistance because it is easy to maintain and the results can be easily reproduced. The application of cell-based models for exploring the pathogenesis of diabetes and insulin resistance as well as for developing drugs for these conditions is well known. However, a comprehensive review of in vitro insulin resistance models is lacking. Therefore, this review was conducted to provide a comprehensive overview and summary of the latest in vitro insulin resistance models, particularly 3T3-L1 (preadipocyte), C2C12 (skeletal muscle), and HepG2 (liver) cell lines induced with palmitic acid, high glucose, or chronic exposure to insulin.

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Insulin‐Mediated PI3K and AKT Signaling

Cited by 4 publications

References 86 publications

The brain as an insulin-sensitive metabolic organ

The brain as an insulin-sensitive metabolic organ

Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation

In Vitro Insulin Resistance Model: A Recent Update

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