Ghrelin rescues palmitate‐induced decrements in insulin signaling in oxidative skeletal muscle from rats
Notice bibliographique
Résumé
Introduction Ghrelin is an orexigenic gastric hormone that also has metabolic effects on insulin‐responsive tissues (eg. skeletal muscle). Existing work from our lab using rat skeletal muscle (unpublished), and others using myoblasts (Han L et al . 2015) demonstrate that ghrelin can stimulate fatty acid oxidation. Our current experimental model is aimed at extending these findings, and determining whether ghrelin can protect against acute, palmitate‐induced impairments in insulin signaling and glucose uptake in skeletal muscle, a major site for insulin‐stimulated glucose disposal. Methods To date, oxidative soleus muscle strips have been isolated from healthy, male Sprague‐Dawley rats and incubated in vials containing pre‐gassed (95% O 2 , 5% CO 2 ) and warmed (30ºC) media. All muscles were equilibrated for 30min, then underwent either low palmitate (0.2mM, LP) or high palmitate (2mM, HP) treatment, with or without acylated (AG) or unacylated (UnAG) ghrelin, for 4h. Muscles were then subjected to either saline or maximal insulin (10mU/ml, 10min) and then snap frozen in liquid nitrogen. Western blots were used to quantify the activation of insulin signaling protein AKT (Ser 473 , Thr 308 ). Results We first confirmed that HP impairs muscle insulin signaling within 4h. Insulin significantly stimulated AKT activation (Ser 473 ) in both palmitate conditions at 1mU/ml (LP: 2.4±0.6; HP: 1.9±0.3) and 10mU/ml (LP: 12.5±1.6; HP: 5.4±0.6) doses. The HP‐induced blunting of AKT phosphorylation was more readily apparent at the maximal insulin concentration; therefore, this was utilized for subsequent incubations to examine the potential effects of ghrelin. For signaling experiments with ghrelin, when compared to control (1.2±0.6), 10mU/ml insulin increased the activation of AKT at both its Ser 473 (LP: 15.3±3.23; HP: 6.86±1.01) and Thr 308 (LP: 12.1±3.17; HP: 7.7±2.05) residues at both palmitate concentrations (p<0.01). Therefore, consistent with our pilot work, 4h of HP exposure significantly reduced insulin's activation of AKT at Ser 473 compared to LP (p<0.01); this trend was present with Thr 308 , but was not significant (p=0.1). Interestingly, AG (14.8±7.6, p<0.05), but not UnAG,(11.2±7.3, p>0.05) was able to preserve Ser 473 AKT activation in the HP condition. Neither AG (8.19±2.32) nor UnAG (5.86±1.20) altered insulin's ability to activate AKT (Thr 308 ) in the context of HP (p>0.05). Conclusions AG preserved insulin's ability to fully activate AKT at its Ser 473 site under HP conditions. Further incubations will be performed to increase statistical power as UnAG trended towards a similar effect, and has been reported to increase insulin sensitivity in the literature. Future measurements will determine whether this alteration to AKT signaling can manifest as a functional change in glucose transport (i.e. whether AG can protect against palmitate‐induced reductions in glucose transport). Also, we will assess ghrelin's effects on (2mM) palmitate oxidation and whether AMPK is involved. These experiments will contribute to the interpretation of both AG and UnAG's effects in skeletal muscle glucose/fatty acid metabolism and insulin signaling. Support or Funding Information DJD is supported by a grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada. DTC holds an NSERC PGS‐D Scholarship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».