I - insulin transfer to mitochondria

Camberos, María del Carmen; Cao, Gabriel; Wanderley, Maria Inês; Udrisar, Daniel P.; Cresto, Juan C.

doi:10.1007/s10863-014-9563-y

Cited by 2 publications

(7 citation statements)

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“…In the citric acid cycle in the mitochondrial matrix, succinate is formed from succinyl-CoA by succinyl-CoA synthetase and is subsequently converted by succinate dehydrogenase to fumarate in the mitochondria; however, succinate can be released to the extracellular space due to local energy metabolism disturbances [ 8 – 10 ]. Under RVH, additional capillaries are formed in the heart to meet the increasing oxygen requirements of the RV; however, the density of the capillaries cannot meet the needs of the RV, and the lower oxygen extraction reserve ultimately makes oxygen utilization less efficient despite the higher demand.…”

Section: Introductionmentioning

confidence: 99%

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

Yang

et al. 2016

PLoS ONE

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BackgroundPulmonary arterial hypertension is characterized by increased pressure overload that leads to right ventricular hypertrophy (RVH). GPR91 is a formerly orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate; however, its role in RVH remains unknown.Methods and ResultsWe investigated the role of succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH induced by pressure overload in SD rats. GPR91 was shown to be located in cardiomyocytes. In the sham and PAB rats, succinate treatment further aggravated RVH, up-regulated RVH-associated genes and increased p-Akt/t-Akt levels in vivo. In vitro, succinate treatment up-regulated the levels of the hypertrophic gene marker anp and p-Akt/t-Akt in cardiomyocytes. All these effects were inhibited by the PI3K antagonist wortmannin both in vivo and in vitro. Finally, we noted that the GPR91-PI3K/Akt axis was also up-regulated compared to that in human RVH.ConclusionsOur findings indicate that succinate-GPR91 signaling may be involved in RVH via PI3K/Akt signaling in vivo and in vitro. Therefore, GPR91 may be a novel therapeutic target for treating pressure overload-induced RVH.

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Section: Introductionmentioning

confidence: 99%

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

Yang

et al. 2016

PLoS ONE

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“…2 and 3) could be interpreted as an increase in insulin turn-over (transfer and degradation) in a more active mitochondrial metabolism. In these conditions, [IDE-Insulin] complex as proposed in a previous paper (Camberos et al 2014) showed a fast insulin accumulation in mitoplasts followed with mitochondrial degradation, more yet with the supplementary diet. Otherwise, the results with high insulin concentrations demonstrated that mitoplasts accumulation was not dependent on insulin concentration.…”

Section: Discussionmentioning

confidence: 68%

“…3.2 Mitoplasts; chromatography of insulin profiles. This experimental part had been published (Camberos et al (Camberos et al 2014)) and it is reproduced with permission of authors. Mitoplasts were solubilized and profiles of Control and IDE were determined through chromatography in Sephadex G50 Superfine (25 ml column) eluted with 1 M acetic acid, 150 mM NaCl, 0.25 % BSA.…”

Section: Resultsmentioning

confidence: 99%

“…These results suggested that insulin induced an endogenous [IDE-Insulin] redistribution into mitochondria, because IDE was not added. The long mitochondrial presequence did not argue against this bution because, as shown, there was an allosteric difficulty in [IDE-Insulin] mitochondrial transfer (Camberos et al 2014), and it could be overcome by insulin excess.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, in confocal studies directed to study SIRT4, it was described that insulin was inside the mitochondria (Haigis et al 2006). In previous study, we observed that IDE facilitates mitochondrial insulin transfer and its accumulation in mitoplasts (Camberos et al 2014). These studies were developed at 25 °C to avoid insulin degradation, because at 37 °C mitochondrial insulin accumulation could not be demonstrated by electron microscopy (Goldfine et al 1981).…”

Section: Introductionmentioning

confidence: 99%

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II - Insulin processing in mitochondria

Camberos

Pérez

Passicot

et al. 2016

J Bioenerg Biomembr

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Our objective was to know how insulin is processing in mitochondria; if IDE is the only participant in mitochondrial insulin degradation and the role of insulin degradation on IDE accumulation in mitoplasts. Mitochondria and its fractions were isolated as described by Greenwalt. IDE was purified and detected in immunoblot with specific antibodies. High insulin degradation was obtained through addition to rat's diet of 25 g/rat of apple and 10 g/rat of hard-boiled eggs, 3 days a week. Mitochondrial insulin degradation was assayed with 5 % TCA, insulin antibody or Sephadex G50 chromatography. Degradation was also assayed 60 min at 37 °C in mitochondrial fractions (IMS and Mx) with diet or not and without IDE. Degradation in fractions precipitated with ammonium sulfates (60-80 %) were studied after mitochondrial insulin incubation (1 ng. insulin during 15 min, at 30 °C) or with addition of 2.5 mM ATP. Supplementary diet increased insulin degradation. High insulin did not increase mitoplasts accumulation and did not decrease mitochondrial degradation. High insulin and inhibition of degradation evidence insulin competition for a putative transport system. Mitochondrial incubation with insulin increased IDE in matrix as observed in immunoblot. ATP decreased degradation in Mx and increased it in IMS. Chromatography of IMS demonstrated an ATP-dependent protease that degraded insulin, similar to described by Sitte et al. Mitochondria participate in insulin degradation and the diet increased it. High insulin did not accomplish mitochondrial decrease of degradation or its accumulation in mitoplasts. Mitochondrial incubation with insulin increased IDE in matrix. ATP suggested being a regulator of mitochondrial insulin degradation.

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I - insulin transfer to mitochondria

Cited by 2 publications

References 31 publications

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

The Succinate Receptor GPR91 Is Involved in Pressure Overload-Induced Ventricular Hypertrophy

II - Insulin processing in mitochondria

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