HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway

Chiefari, Eusebio; Nevolo, Maria T.; Arcidiacono, Biagio; Maurizio, E; Nocera, Aurora; Iiritano, Stefania; Sgarra, Riccardo; Possidente, Katiuscia; Palmieri, Camillo; Paonessa, Francesco; Brunetti, Giuseppe; Manfioletti, Guidalberto; Foti, Daniela; Brunetti, Antonio

doi:10.1038/srep00251

Cited by 52 publications

(61 citation statements)

References 41 publications

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“…A fasting-induced interaction, mediated by insulin signaling, with members of the FOXO family and RXR has been described as well43. HMGA1 is a downstream target of the insulin receptor pathway and could function as an important nuclear factor mediating the binding of FOXO proteins to other nuclear receptors, including the retinoid nuclear receptor family and thereby regulating insulin target genes44.…”

Section: Discussionmentioning

confidence: 99%

A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction

Jongbloed

Saat

Verweij

et al. 2017

Sci Rep

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During kidney transplantation, ischemia-reperfusion injury (IRI) induces oxidative stress. Short-term preoperative 30% dietary restriction (DR) and 3-day fasting protect against renal IRI. We investigated the contribution of macronutrients to this protection on both phenotypical and transcriptional levels. Male C57BL/6 mice were fed control food ad libitum, underwent two weeks of 30%DR, 3-day fasting, or received a protein-, carbohydrate- or fat-free diet for various periods of time. After completion of each diet, renal gene expression was investigated using microarrays. After induction of renal IRI by clamping the renal pedicles, animals were monitored seven days postoperatively for signs of IRI. In addition to 3-day fasting and two weeks 30%DR, three days of a protein-free diet protected against renal IRI as well, whereas the other diets did not. Gene expression patterns significantly overlapped between all diets except the fat-free diet. Detailed meta-analysis showed involvement of nuclear receptor signaling via transcription factors, including FOXO3, HNF4A and HMGA1. In conclusion, three days of a protein-free diet is sufficient to induce protection against renal IRI similar to 3-day fasting and two weeks of 30%DR. The elucidated network of common protective pathways and transcription factors further improves our mechanistic insight into the increased stress resistance induced by short-term DR.

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Section: Discussionmentioning

confidence: 99%

A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction

Jongbloed

Saat

Verweij

et al. 2017

Sci Rep

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“…6B) to suppress the expression of PEPCK -or of glucose-6-phosphatase -is largely attributable to activation of a PI3K/akt-dependent signal pathway and downstream phosphorylation and inhibition of the forkhead box protein O1/A2 transcription factor (Fox01) and the transducer of regulated cAMP response element binding protein (CREB) activity 2 (TORC2) [125][126][127][128][129][130]. Recent evidence also implicates the high-mobility AT-hook 1 (HMGA1) nuclear factor in hepatic PI3K-mediated effects of insulin [131]. Glucagon elicits opposite effects on the expressions of many of the same enzymes and cofactors.…”

Section: Transcriptional Regulation Of Phosphoenolpyruvate Carboxykinasementioning

confidence: 95%

Glucagon and Cyclic AMP: Time to Turn the Page?

Rodgers

2012

CDR

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It is well established that glucagon can stimulate adipose lipolysis, myocardial contractility, and hepatic glucose output by activating a GPCR and adenylate cyclase (AC) and increasing cAMP production. It is also widely reported that activation of AC in all three tissues requires pharmacological levels of the hormone, exceeding 0.1 nM. Extensive evidence is presented here supporting the view that cAMP does not mediate metabolic actions of glucagon on adipose, heart, or liver in vivo. Only pharmacological levels stimulate AC, adipose lipolysis, or cardiac contractility. Physiological concentrations of glucagon (below 0.1 nM) duplicate metabolic effects of insulin on the heart by activating a PI3K-dependent signal without stimulating AC. In the liver, glucagon can enhance gluconeogenesis and glucose output -by increasing the expression of PEPCK or inhibiting the activity of PK -at pharmacological concentrations by activating AC coupled to a low-affinity GPCR, but also at physiological concentrations by activating a high affinity receptor without generating cAMP. Plausible AC/cAMP-independent signals mediating the increase in gluconeogenesis include p38 MAPK (PEPCK expression) and IP3/DAG/Ca 2+ (PK activity). None of glucagon's physiological effects can be explained by activation of spare receptors or amplification of the AC/cAMP signal. In a new model proposed here, glucagon antagonizes insulin on the liver but mimics insulin on the heart without activating AC. Confirmation of the model would have broad implications, applicable not only to the general field of metabolic endocrinology but also to the specific role of glucagon in the pathogenesis and treatment of diabetes.

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“…Our data suggest that the IVS5-13insC variant is not associated with DR in this Chinese T2DM cohort. Previous study represented that HMGA1 is the key regulator of the expression of the INSR, the major component of insulin signaling pathway.- 25 Individuals with defects in HMGA1 gene have decreased INSR expression and increased susceptibility to T2DM. 24,25 However, no correlation was shown on the IVS5-13insC variant in HMGA1 gene and the risk of DR in this Chinese T2DM population.…”

Section: Discussionmentioning

confidence: 99%

Association of ICAM-1 and HMGA1 Gene Variants with Retinopathy in Type 2 Diabetes Mellitus Among Chinese Individuals

et al. 2015

Current Eye Research

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HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway

Cited by 52 publications

References 41 publications

A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction

A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction

Glucagon and Cyclic AMP: Time to Turn the Page?

Association of ICAM-1 and HMGA1 Gene Variants with Retinopathy in Type 2 Diabetes Mellitus Among Chinese Individuals

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