GIP Signaling Integrates with Insulin Signaling to Regulate Glucose and Lipid Metabolism in Human Adipocytes

MicroRNAs (miRNAs) are small non-coding RNAs that participate in heart development and pathological processes mainly by silencing gene expression. Overwhelming evidence has suggested that miRNAs were involved in various cardiovascular pathological processes, including arrhythmias, ischemia-reperfusion injuries, dysregulation of angiogenesis, mitochondrial abnormalities, fibrosis, and maladaptive remodeling. Various miRNAs could regulate myocardial contractility, vascular proliferation, and mitochondrial function. Meanwhile, it was reported that miRNAs could manipulate nutrition metabolism, especially glucose and lipid metabolism, by regulating insulin signaling pathways, energy substrate transport/metabolism. Recently, increasing studies suggested that the abnormal glucose and lipid metabolism were closely associated with a broad spectrum of cardiovascular diseases (CVDs). Therefore, maintaining glucose and lipid metabolism homeostasis in the heart might be beneficial to CVD patients. In this review, we summarized the present knowledge of the functions of miRNAs in regulating cardiac glucose and lipid metabolism, as well as highlighted the miRNA-based therapies targeting cardiac glucose and lipid metabolism.

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Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00323.2020 ◽

2020 ◽

Vol 319 (4) ◽

pp. E721-E733

Author(s):

Paul J. Rozance ◽

Amanda K. Jones ◽

Stephanie L. Bourque ◽

Angelo D’Alessandro ◽

William. W. Hay ◽

...

Keyword(s):

Lipid Metabolism ◽

Amino Acid ◽

Insulin Signaling ◽

Carbon Metabolism ◽

Fetal Liver ◽

Whole Body ◽

Ampk Activation ◽

Fetal Sheep ◽

Glucose And Lipid Metabolism ◽

One Carbon Metabolism

The effect of chronic of hyperinsulinemia in the fetal liver is poorly understood. Here, we produced hyperinsulinemia with euglycemia for ∼8 days in fetal sheep [hyperinsulinemic (INS)] at 0.9 gestation. INS fetuses had increased insulin and decreased oxygen and amino acid (AA) concentrations compared with saline-infused fetuses [control (CON)]. Glucose (whole body) utilization rates were increased, as expected, in INS fetuses. In the liver, however, there were few differences in genes and metabolites related to glucose and lipid metabolism and no activation of insulin signaling proteins (Akt and mTOR). There was increased p-AMPK activation and decreased mitochondrial mass ( PGC1A expression, mitochondrial DNA content) in INS livers. Using an unbiased multivariate analysis with 162 metabolites, we identified effects on AA and one-carbon metabolism in the INS liver. Expression of the transaminase BCAT2 and glutaminase genes GLS1 and GLS2 was decreased, supporting decreased AA utilization. We further evaluated the roles of hyperinsulinemia and hypoxemia, both present in INS fetuses, on outcomes in the liver. Expression of PGC1A correlated only with hyperinsulinemia, p-AMPK correlated only with hypoxemia, and other genes and metabolites correlated with both hyperinsulinemia and hypoxemia. In fetal hepatocytes, acute treatment with insulin activated p-Akt and decreased PGC1A, whereas hypoxia activated p-AMPK. Overall, chronic hyperinsulinemia produced greater effects on amino acid metabolism compared with glucose and lipid metabolism and a novel effect on one-carbon metabolism in the fetal liver. These hepatic metabolic responses may result from the downregulation of insulin signaling and antagonistic effects of hypoxemia-induced AMPK activation that develop with chronic hyperinsulinemia.

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Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome

Open Chemistry ◽

10.1515/chem-2019-0130 ◽

2019 ◽

Vol 17 (1) ◽

pp. 1213-1221

Author(s):

Chu Shufang ◽

Zhou Yinan ◽

Li Huilin ◽

Zhao Hengxia ◽

Liu Deliang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Lipid Metabolism ◽

Insulin Signaling ◽

Blood Stasis ◽

Blood Stasis Syndrome ◽

Glucose And Lipid Metabolism

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

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Faculty Opinions recommendation of Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718109960.793490091 ◽

2014 ◽

Author(s):

Ji-Zeng Du ◽

Xue-Qun Chen

Keyword(s):

Lipid Metabolism ◽

Cross Talk ◽

Insulin Signaling ◽

Glucose And Lipid Metabolism ◽

Hepatic Glucose

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Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes

Nature Medicine ◽

10.1038/nm.3294 ◽

2013 ◽

Vol 19 (10) ◽

pp. 1325-1330 ◽

Cited By ~ 82

Author(s):

Cullen M Taniguchi ◽

Elizabeth C Finger ◽

Adam J Krieg ◽

Colleen Wu ◽

Anh N Diep ◽

...

Keyword(s):

Lipid Metabolism ◽

Cross Talk ◽

Insulin Signaling ◽

Glucose And Lipid Metabolism ◽

Hepatic Glucose

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FoxO integration of insulin signaling with glucose and lipid metabolism

Journal of Endocrinology ◽

10.1530/joe-17-0002 ◽

2017 ◽

Vol 233 (2) ◽

pp. R67-R79 ◽

Cited By ~ 68

Author(s):

Sojin Lee ◽

H Henry Dong

Keyword(s):

Lipid Metabolism ◽

Insulin Signaling ◽

Target Genes ◽

Therapeutic Option ◽

Cell Metabolism ◽

The Body ◽

Glucose And Lipid Metabolism ◽

Forkhead Box ◽

Neurodegeneration Disease

The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA-binding domain, known as ‘forkhead box’ domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals. Of the FoxO family, FoxO6 is the least characterized member and is shown to play pivotal roles in the liver, skeletal muscle and brain. Altered FoxO6 expression is associated with the pathogenesis of insulin resistance, dietary obesity and type 2 diabetes and risk of neurodegeneration disease. FoxO6 is evolutionally divergent from other FoxO isoforms. FoxO6 mediates insulin action on target genes in a mechanism that is fundamentally different from other FoxO members. Here, we focus our review on the role of FoxO6, in contrast with other FoxO isoforms, in health and disease. We review the distinctive mechanism by which FoxO6 integrates insulin signaling to hepatic glucose and lipid metabolism. We highlight the importance of FoxO6 dysregulation in the dual pathogenesis of fasting hyperglycemia and hyperlipidemia in diabetes. We review the role of FoxO6 in memory consolidation and its contribution to neurodegeneration disease and aging. We discuss the potential therapeutic option of pharmacological FoxO6 inhibition for improving glucose and lipid metabolism in diabetes.

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