MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway

MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs in eukaryotes, have been recognized as significant regulators of gene expression through post-transcriptional mechanisms. To date, >2000 miRNAs have been identified in the human genome, and they orchestrate a variety of biological and pathological processes. Disruption of miRNA levels correlates with many diseases, including diabetes mellitus, a complex multifactorial metabolic disorder affecting >400 million people worldwide. miRNAs are involved in the pathogenesis of diabetes mellitus by affecting pancreatic β-cell functions, insulin resistance, or both. In this review, we summarize the investigations of the regulatory roles of important miRNAs in diabetes, as well as the potential of circulating miRNAs as diagnostic markers for diabetes mellitus.

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“…Therefore, miRNAs targeting PTEN such as miR-499 , miR-26b , and miR-301a are beneficial for improving insulin sensitivity [49,50,51]. …”

Section: Mirnas and Insulin Resistance (Ir)mentioning

confidence: 99%

Regulatory Roles of MicroRNAs in Diabetes

Feng

Xing

Xie

2016

IJMS

122

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“…Obese prediabetic subjects have been reported to have 400-600 pM/L serum insulin and 7-11 mmol/L of blood glucose (Dileepan & Feldt 2013). Recently, Guanfeng Xu and coworkers exposed human primary adipocytes to 600 pM insulin/25 mM glucose for 48 h to induce insulin resistance (Xu et al 2015). This inspired us to develop IR adipocyte model by decreasing the insulin exposure concentration to 500 pM and glucose 10 mM for 72 h to corroborate with pathophysiological level.…”

Section: Figurementioning

confidence: 99%

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

Rajan

Shankar

Beg

et al. 2016

Journal of Endocrinology

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The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8 weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes.

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“…However, in this study we did not examine the effects of miR‐26b on the expressions of other Bcl‐2 family members. Additionally, according to previous literature, miR‐26b can regulate multiple upstream signaling pathways of mitochondrial‐mediated apoptosis, including the NF‐κB/MMP‐9/VEGF, PTEN/PI3K/AKT, and COX‐2 pathways [21,37–39]. These activities, we assume, would also be involved in the underlying mechanism of action regarding the anti‐tumorigenic effects of miR‐26b.…”

Section: Discussionmentioning

confidence: 84%

MicroRNA‐26b suppresses tumorigenicity and promotes apoptosis in small cell lung cancer cells by targeting myeloid cell leukemia 1 protein

Shi

2018

The Kaohsiung J of Med Scie

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The aim of this study was to investigate the role of microRNA‐26b (miR‐26b) in regulating the proliferation, migration, and apoptosis of small cell lung cancer (SCLC) cells. First, we examined the expression level of miR‐26b in human normal fetal lung fibroblasts (NFLFs) and three SCLC cell lines NCI‐H466, NCI‐H1688, and NCI‐H196. In the following experiments, the three SCLC cell lines were transfected with miR‐26b mimic and inhibitor. Cell growth and survival, as well as migration and invasion capacities were determined by MTT, colony formation, Transwell migration and invasion, and wound healing assays. Cell apoptosis, production of reactive oxygen species, and mitochondrial membrane potential were also measured in the three cell lines following various treatments. As a result, we found that the level of miR‐26b was significantly lower in SCLC cells than in NFLFs. Additionally, transfection with miR‐26b mimic could inhibit proliferation, colony formation, and migration, as well as induce apoptosis in these SCLC cell lines; while miR‐26b inhibitor showed the opposite effects. Further mechanistic experiment revealed that miR‐26b could suppress the expression of myeloid cell leukemia 1 protein (Mcl‐1) and the 3′‐untranslated region (3′‐UTR) of Mcl‐1 may be the direct binding site of miR‐26b, suggesting that the effect of miR‐26b may be mediated by targeting Mcl‐1. Collectively, our findings offer a new insight into the role of miR‐26b in the pathogenesis of SCLC, and provide primary evidence supporting the potential of miR‐26b‐based therapy for the treatment of SCLC.

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MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway

Abstract: Decreased miR-26b expression in VAT may be involved in obesity-related IR by interrupting the PTEN/PI3K/AKT pathway.

Cited by 73 publications

References 47 publications

Regulatory Roles of MicroRNAs in Diabetes

Regulatory Roles of MicroRNAs in Diabetes

Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte

MicroRNA‐26b suppresses tumorigenicity and promotes apoptosis in small cell lung cancer cells by targeting myeloid cell leukemia 1 protein

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