A polymorphism of HMGA1 is associated with increased risk of metabolic syndrome and related components

Chiefari, Eusebio; Tanyolaç, Sinan; Iiritano, Stefania; Sciacqua, Angela; Capula, Carmelo; Arcidiacono, Biagio; Nocera, Aurora; Possidente, Katiuscia; Baudi, Francesco; Ventura, Valeria; Brunetti, Giuseppe; Brunetti, Francesco; Vero, Raffaella; Maio, Raffaele; Greco, Manfredi; Pavia, Maria; Hodoğlugil, Uğur; Durlach, V.; Pullinger, Clive R.; Goldfine, Ira D.; Perticone, Francesco; Foti, Daniela; Brunetti, Antonio

doi:10.1038/srep01491

Cited by 50 publications

(38 citation statements)

References 49 publications

(70 reference statements)

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“…In this respect, Calabria, Southern Italy, is often given as an example of a genetically homogeneous population that differs from other populations with more genetic diversity. 11,12 Although further studies with different populations and larger sample size would be useful to corroborate this observation, our findings that gender may moderate responses to liraglutide (and perhaps other pharmacological agents) are in line with existing studies revealing several differences between women and men with diabetes and other diseases. 13 Weight loss in the liraglutide group and the parallel decrease of WC that we observed are consistent with other reports 5 and with the demonstration that weight loss with liraglutide is primarily as a result of a reduction in fat tissue.…”

Section: Discussionsupporting

confidence: 91%

Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy

Chiefari

Capula

Vero

et al. 2015

Diabetes Technology & Therapeutics

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Section: Discussionsupporting

confidence: 91%

Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy

Chiefari

Capula

Vero

et al. 2015

Diabetes Technology & Therapeutics

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“…LL, constant light. bility of the "enhanceosome," which in turn drives transcription (7). In recent years, the Hmga1 gene has been associated with insulin resistance and Type 2 diabetes (7).…”

Section: Discussionmentioning

confidence: 99%

Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver

Spichiger

Torres-Farfán

Galdames

et al. 2015

Physiological Genomics

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Recent reports account for altered metabolism in adult offspring from pregnancy subjected to abnormal photoperiod, suggesting fetal programming of liver physiology. To generate a pipeline of subsequent mechanistic experiments addressing strong candidate genes, here we investigated the effects of constant gestational light on the fetal liver transcriptome. At 10 days of gestation, dams were randomized in two groups ( n = 7 each): constant light (LL) and normal photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated from the fetal liver and subjected to DNA microarray (Affymetrix platform for 28,000 genes). Selected differential mRNAs were validated by quantitative PCR (qPCR), while integrated transcriptional changes were analyzed with Ingenuity Pathway Analysis and other bioinformatics tools. Comparison of LL relative to LD fetal liver led to the following findings. Significant differential expression was found for 3,431 transcripts (1,960 upregulated and 1,471 downregulated), with 393 of them displaying ≥ 1.5-fold change. We validated 27 selected transcripts by qPCR, which displayed fold-change values highly correlated with microarray ( r2 = 0.91). Different markers of nonalcoholic fatty liver disease were either upregulated (e.g., Ndn and Pnpla3) or downregulated (e.g., Gnmt, Bhmt1/2, Sult1a1, Mpo, and Mat1a). Diverse pathways were altered, including hematopoiesis, coagulation cascade, complement system, and carbohydrate and lipid metabolism. The microRNAs 7a-1, 431, 146a, and 153 were upregulated, while the abundant hepatic miRNA 122 was downregulated. Constant gestational light induced extensive modification of the fetal liver transcriptome. A number of differentially expressed transcripts belong to fundamental functional pathways, potentially contributing to long-term liver disease.

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“…IR overexpression in cancer cells is a possible consequence of increased HMGA1 protein [30,31], a transcription factor that regulates gene expression and specifically inactivates p53, an oncogene suppressor. P53 suppresses the promoter activity of the IR and IGF-1R, and its inactivation increases the cellular content of the IR.…”

Section: The Insulin Receptor and Cancer Cellsmentioning

confidence: 99%

Insulin, insulin receptors, and cancer

Vigneri

Goldfine

Frittitta

2016

J Endocrinol Invest

184

147

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Insulin is a major regulator of cell metabolism but, in addition, is also a growth factor. Insulin effects in target cells are mediated by the insulin receptor (IR), a transmembrane protein with enzymatic (tyrosine kinase) activity. The insulin receptor, however, is represented by a heterogeneous family of proteins, including two different IR isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate IGF-1 receptor. These different receptors may bind insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many cancer cells require insulin for optimal in vitro growth. Recent data indicate that: (1) insulin stimulates growth mainly via its own receptor and not the IGF-1 receptor; (2) in many cancer cells, the IR is overexpressed and the A isoform, which has a predominant mitogenic effect, is more represented than the B isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to insulin. For this reason, all conditions of hyperinsulinemia, both endogenous (prediabetes, metabolic syndrome, obesity, type 2 diabetes before pancreas exhaustion and polycystic ovary syndrome) and exogenous (type 1 diabetes) will increase the risk of cancer. Cancer-related mortality is also increased in patients exposed to hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with hyperinsulinemia and their therapies does not allow a precise evaluation of the cancer-promoting effect of hyperinsulinemia, but its detrimental effect on cancer incidence and mortality is well documented.

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A polymorphism of HMGA1 is associated with increased risk of metabolic syndrome and related components

Cited by 50 publications

References 49 publications

Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy

Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy

Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver

Insulin, insulin receptors, and cancer

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