Ghrelin and the Regulation of Peripheral Tissue Metabolism
Notice bibliographique
Résumé
Introduction Ghrelin is a potent, appetite‐ and growth hormone (GH) ‐stimulating gastric hormone that has been recently shown to have important metabolic effects on insulin‐responsive peripheral tissues (eg. adipose tissue, skeletal muscle). Ghrelin increases exponentially prior to a meal, and rapidly declines to baseline after meal consumption. Therefore, it is important to elucidate any potential role that ghrelin may have in mediating carbohydrate and lipid metabolism surrounding entrained meal time. There is evidence, albeit limited, to suggest that both acylated (AG) and deacylated (DAG) ghrelin may act to potentiate glucose uptake in myocytes and inhibit the adrenergic stimulation of lipolysis in isolated adipocytes. Conversely, upon in vivo administration of ghrelin in humans, there is a marked decrease in insulin sensitivity and increases in local (adipose and skeletal muscle) indicators of lipolysis (glycerol). However, in vivo findings are confounded by factors such as the secondary increase in growth hormone, which can in itself stimulate lipolysis and influence glucose uptake. Methods Soleus (oxidative) and extensor digitorum longus (EDL, glycolytic) muscles, and subcutaneous (inguinal ‐ iWAT) and visceral (retroperitoneal ‐ RP) adipose tissue depots were isolated from male Sprague Dawley rats. Muscles were incubated in the presence of labelled 3‐methyl‐O‐glucose to assess the effect of AG and DAG (5 to 150 nM) on basal and insulin stimulated glucose uptake. Adipose tissue organ culture was used to assess glycerol release (index of lipolysis) following incubation with either vehicle, the beta‐3 agonist CL 316 243 (10uM), CL + AG (50nM), CL + DAG (50nM) or AG and DAG independently. Results AG and DAG had a no direct influence on basal (Con: 62 ± 9; AG: 56 ± 5; DAG: 78 ± 13 nmol/g/5min) or insulin‐stimulated (Con: 41 ± 3; Ins: 82 ± 5; Ins+AG: 65 ± 11; Ins+DAG: 94 ± 9 nmol/g/5min) glucose uptake in soleus (shown) or EDL skeletal muscle. The activation of insulin signaling protein pAkt (Ser 473 ) was also unchanged by ghrelin treatment. Compared to vehicle (iWAT: 0.54 ± 0.05; RP: 0.56 ± 0.08 mM/g) CL markedly increased rates of glycerol release in both iWAT (1.20 ± 0.06) and RP (1.91 ± 0.30) depots (p<0.05). This effect was abolished in the presence of both AG (iWAT: 0.79 ± 0.09; RP: 1.52 ± 0.12) and DAG (iWAT: 0.82 ± 0.05; RP: 1.44 ± 0.19) (p>0.05). AG (iWAT: 0.48 ± 0.08; RP: 0.54 ± 0.08) and DAG (iWAT: 0.62 ± 0.14; RP: 0.54 ± 0.09) did not independently affect glycerol release. These effects were observed following both 2h (shown) and 4h of treatment. Conclusions Ghrelin isoforms have no direct effect on skeletal muscle glucose uptake, but do inhibit adrenergic‐stimulated lipolysis in both subcutaneous and visceral adipose depots. Further work will consider whether ghrelin can act as a regulator of lipolysis in conjunction with other known pre and postprandial hormones (eg. GH, insulin). Finally, ghrelin action on cellular signaling underlying functional changes in lipolysis will be assessed (eg. HSL, ATGL, perilipin). These experiments will contribute to the accurate interpretation of AG and DAG's direct effects in peripheral tissue glucose and lipid metabolism. Support or Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
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 ».