Supranutritional selenium intake from enriched milk casein impairs hepatic insulin sensitivity via attenuated IRS/PI3K/AKT signaling and decreased PGC-1α expression in male Sprague–Dawley rats

Stahel, Priska; Kim, Julie; Cieslar, S.R.L.; Warrington, Jenny; Xiao, Changting; Cant, J.P.

doi:10.1016/j.jnutbio.2016.12.012

Cited by 19 publications

(14 citation statements)

References 41 publications

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“…Various antidiabetic constituents, such as flavonoids and ellagitannins, attenuate hepatic insulin resistance through regulation of the PI3K/Akt signaling pathway in vivo and in vitro (Huang, Chang, Wu, Shih, & Shen, 2016; Li et al., 2019; Mokashi, Khanna, & Pandita, 2017). Recognized as a key pathway to regulate glucose metabolism, interference with this pathway has been shown to lead to reduced glycogen synthesis and increased gluconeogenesis in the liver of T2DM rats (Stahel et al., 2017; Wang et al., 2018). As a mediator of insulin response upstream of PI3K, IRS‐2 plays a central role in preserving insulin activity in multiple cell types, whereas its deficiency may represent a fundamental cause of the development of insulin resistance and consequent β‐cell failure as a compensatory mechanism (Brady, 2004; Kadowaki, 2000).…”

Section: Resultsmentioning

confidence: 99%

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Xin

Zhang

et al. 2020

Journal of Food Science

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We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)-and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3β phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM.Keywords: Aronia melanocarpa berry, hepatic insulin resistance, PI3K/Akt signaling pathway, type 2 diabetes mellitus Practical Application: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.

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Section: Resultsmentioning

confidence: 99%

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Xin

Zhang

et al. 2020

Journal of Food Science

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“…This fits with the observation that both maximal expression of selenoproteins and selenoprotein deficiency promoted development of a T2DM-like phenotype in mice [ 99 ]. Though dietary supplementation with Se at supranutritional doses can also affect functioning and secretion of insulin, the corresponding alterations in signaling and metabolic pathways are often more subtle and do not necessarily induce diabetes [ 99 , [101] , [102] , [103] , [104] , [105] , [106] ]. Interestingly, maternal Se status may predispose the offspring to metabolic disorders: diabetes-like phenotypes associated with either insulin deficiency or resistance were observed in rat pups, depending on whether the dams received Se-deficient or high-Se diets during gestation and lactation [ 107 ].…”

Section: What Can We Learn From Animal Studies About a Link Between S...mentioning

confidence: 99%

“…Taken together, both very low and high Se intake in addition to deficient or supraphysiological selenoprotein biosynthesis/activity can promote or exacerbate metabolic derangement. Nevertheless, marginal Se deficiency or oversupply (as also occurs in humans) does not generate overt diabetes/MetS [ 4 , [97] , [98] , [99] , [100] , [101] , [102] , [103] , [104] , [105] , [106] , [107] , [108] , [109] ].…”

Section: What Can We Learn From Animal Studies About a Link Between S...mentioning

confidence: 99%

The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities

2022

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“…AMPK binds to and activates PGC-1α by direct phosphorylation on Thr117 and Ser538. Nevertheless unlike p38 MAPK and AMPK, the kinase activity of Akt and GSK3β is associated with the inhibition of PGC-1α [33][34][35][36]. Akt abrogates PGC-1α by either direct phosphorylation at Ser570 [31] or inducing CDC like kinase 2 (Clk2), which, in turn, phosphorylates and downregulates PGC-1α activity [37].…”

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confidence: 99%

PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

Rius‐Pérez

Torres-Cuevas

Millán

et al. 2020

Oxidative Medicine and Cellular Longevity

432

292

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Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

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Supranutritional selenium intake from enriched milk casein impairs hepatic insulin sensitivity via attenuated IRS/PI3K/AKT signaling and decreased PGC-1α expression in male Sprague–Dawley rats

Cited by 19 publications

References 41 publications

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats

The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities

PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

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