The functional duality of SGK1 in the regulation of hyperglycemia

Yang, Chunliang; Li, Junyi; Sun, Fei; Zhou, Haifeng; Yang, Jia; Yang, Chao

doi:10.1530/ec-20-0225

Cited by 12 publications

(7 citation statements)

References 70 publications

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“…SGK1, a serine/threonine that is kinase-dependent on phosphatidylinositol 3-kinase, is expressed in many tissue types and induced by several hormones, such as glucocorticoids and androgens [ 22 ]. SGK1 has been shown to regulate glucose levels [ 23 ], affect various physiological functions, and plays an active role in the pathophysiology of obesity, diabetes, autoimmune diseases, and cancer [ 23 ]. SGK1 expression is upregulated in some tumors, such as breast cancer [ 24 ], multiple myelomas [ 25 ], and lung cancer, and it is downregulated in others, such as prostate cancer [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer

Al-Alem,

Rauscher,

Alem

et al. 2023

Cancers

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It is crucial to understand molecular alterations in breast cancer and how they relate to clinicopathologic factors. We have previously shown that the glucocorticoid receptor (GCR) protein expression was reduced in invasive breast carcinoma compared to normal breast tissue. Glucocorticoids, signaling through the GCR, regulate several cellular processes via downstream targets such as serum/glucocorticoid-regulated kinase 1 (SGK1) and B-cell lymphoma 2 (Bcl-2). We measured the expression of SGK1 and Bcl-2, in respective breast cancer tissue arrays, from a multiracial cohort of breast cancer patients. Higher cytoplasmic SGK1 staining was stronger in breast cancer tissue compared to normal tissue, especially in hormone receptor-negative cases. Conversely, the expression of cytoplasmic Bcl-2 was reduced in breast cancer compared to normal tissue, especially in hormone receptor-negative cases. Bcl-2 staining was associated with the self-reported racial/ethnic category, an earlier clinical stage, a lower histological grade, and a higher survival rate. Bcl-2 expression was associated with longer survival in models adjusted for age and race (HR = 0.32, 95% CI: 0.15, 0.65), and Bcl-2 expression remained strongly positively associated with protection from breast cancer death, with additional adjustments for ER/PR status (HR = 0.41, 95% CI: 0.2, 0.85). SGK1 and Bcl-2 may play biological roles in breast cancer development and/or progression.

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Section: Discussionmentioning

confidence: 99%

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer

Al-Alem,

Rauscher,

Alem

et al. 2023

Cancers

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“…SGK 1 phosphorylation of FOXO1 and FOXO3 via PI3K/Akt signaling pathway. SGK1 affect many multiple physiologic processes via phosphorylation of downstream proteins [49][50][51]. SGK1 promotes adipocyte differentiation and controls cell proliferation by regulating the phosphorylation level of FOXO1 and FOXO3, respectively [52,53].…”

Section: Discussionmentioning

confidence: 99%

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

Lei

Wei

Tang

et al. 2022

Preprint

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Background: Improving the intramuscular fat content of beef not only could improve our living standard, but decrease the the risk of the disease from the aspect of human nutrition and diet. Serum/glucocorticoid-inducible kinase 1 (SGK1) is a critical kinase involved in regulating multiple metabolic processes. Results: In the present study we reveal the molecular mechanism by which SGK1 affects the phosphorylation of FOXO1 and FOXO3 thus regulating bovine fat deposition via the PI3K/Akt signaling pathway. SGK1 was characterized primarily in the bovine kidney, where it peaked at day 6 of preadipocyte differentiation. Overexpression of SGK1 in bovine preadipocytes promoted mRNA expression of adipose-specific genes, while cell cycle-related genes were repressed. Adipocyte differentiation-related proteins were not significantly changed, but proliferation-related proteins were markedly inhibited. Moreover, mRNA expression of adipose-specific genes were down-regulated while cell cycle-related genes were up-regulated in response to loss-of-function SGK1. The expression of adipose differentiation-related proteins were significantly inhibited but proliferation-related proteins were not significantly changed. Overexpression of SGK1 in bovine adipocytes significantly changed the gene expression enriched in the PI3K/Akt signaling pathways through RNA-seq. Subsequently, we found that overexpression of SGK1 increased phosphorylation of FOXO1/FOXO3 and reduced protein expression, whereas SGK1 deletion had opposite effects. Overall, we show that overexpression of SGK1 promotes adipogenesis mainly via inhibiting preadipocyte proliferation, whereas the loss-of-function of SGK1 represses adipogenesis mainly through inhibition of adipocyte differentiation. Mechanistically, SGK1 changes the phosphorylation of two key genes located downstream in the PI3K/Akt signaling pathway, FOXO1/FOXO3, thus promoting fat deposition in cattle. Conclusion: These data reveal that SGK1 is a positively regulatory during intramuscular adipogenesis of cattle, which expands the candidates regulating bovine adipogenesis and provides the security for human healthy from the aspect of high-quality beef.

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“…SGK1 affected multiple physiologic processes via phosphorylation of downstream proteins [43][44][45]. SGK1 overexpression improved the hypercholesterolemic induced by diet or genetically obese due to disorder of lipid metabolism in mice [46].…”

Section: Sgk1 Affects the Phosphorylation And Expression Of Foxo1 And...mentioning

confidence: 99%

SGK1 affects bovine adipocyte proliferation and differentiation via regulation of the PI3K/Akt signaling pathway

Lei

Pan

Wei

et al. 2022

Preprint

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Objectives: Serum/glucocorticoid-inducible kinase 1 (SGK1) gene encodes a serine/threonine protein kinase that plays an essential role in cellular stress response and regulation of multiple metabolic processes. However, its role in bovine adipogenesis remains unknown. In this study, we aimed to clarify the role of SGK1 on bovine preadipocyte differentiation. Materials and Methods: Preadipocytes were induced to differentiation to detect the temporal expression pattern of SGK1. Heart, liver, lung, spleen, kidney, muscle and fat tissues were collected to detect its tissue expression profile. Recombinant adenovirus and the lentivirus were packaged for overexpression and knockdown. Oil Red O staining, quantitative real-time PCR, Western blot analysis, Yeast two-hybrid assay, and RNA-seq were performed to study the regulatory mechanism of SGK1. Results: SGK1 showed significantly higher expression in adipose and revealed significantly induced expression in differentiated adipocytes. Furthermore, overexpression of SGK1 greatly promoted adipogenesis and inhibited proliferation, which could be shown by the remarkable increasement of lipid droplet, and the expression levels of adipogenic marker genes and cell cycle-related genes. Inversely, its knockdown inhibited adipogenesis and facilitated proliferation. Mechanistically, SGK1 regulates the phosphorylation and expression of two critical genes located in the downstream of PI3K/Akt signaling pathway, FOXO1/FOXO3, thus promoting adipogenesis and inhibiting proliferation in cattle. Conclusions: SGK1 is required for bovinepreadipocyte proliferation and differentiation, which contributes to a better understanding of fat deposition in cattle.

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The functional duality of SGK1 in the regulation of hyperglycemia

Cited by 12 publications

References 70 publications

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer

SGK1 Affects the Phosphorylation of FOXO1/FOXO3 Promoting Bovine Fat Deposition via the PI3K/Akt Signaling Pathway

SGK1 affects bovine adipocyte proliferation and differentiation via regulation of the PI3K/Akt signaling pathway

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