Pancreatic islet-specific overexpression of reg3β protein
Notice bibliographique
Résumé
Reg family proteins have been implicated in islet β-cell proliferation, survival, and regeneration. Reg3β (pancreatitis-associated protein, PAP; or gene expressed in hepatocellular carcinoma-intestine-pancreas, HIP) was first reported as a pancreatic secretory protein expressed in acinar cells during the acute phase of pancreatitis. Previous studies in Dr. Liu's and other research groups have demonstrated that Reg3β was specifically induced either during islet hyperplasia in the IGF-I-deficient pancreas or as a result of GLP-1-induced islet cell growth. Reg3β has been shown to play anti-apoptotic and anti-inflammatory roles during acute pancreatitis. In the present study, we generated transgenic mice with pancreatic β-cell-specific over-expression of Reg3β and investigated the effect of Reg3β in the regulation of β-cell function during streptozotocin (STZ)-induced type 1 diabetes (T1D) and diet-induced type 2 diabetes (T2D). The data presented in Chapter II demonstrated that pancreatic islet-specific overexpression of Reg3β protein protected mice from STZ-induced T1D. The RIP-I/Reg3β mice were indistinguishable from wild-type littermates in fertility, islet morphology, β-cell mass, and insulin secretion response, yet were slightly high in glucose and low in the expression of Glut2 and insulin. These transgenic mice were significantly protected from STZ-induced hyperglycemia and weight loss that were observed in the wild-type controls. To identify the molecular networks that Reg3β is involved in, a whole genome DNA microarray analysis of isolated islet RNA samples revealed more than 45 genes whose expression were markedly up- or down-regulated as a consequence of Reg3β overexpression. We further confirmed the change in several genes, including the upregulation of islet-protective osteopontin/Spp1 and acute responsive nuclear protein Nupr1/p8 by real-time PCR, Western blots and histology. These results support the potential of Reg3β in preventing STZ-induced damage by regulating expression of specific genes.In Chapter III, mice carrying Reg3β over-expression displayed worsened T2D induced by high-fat diet (HFD), as characterized by faster and more severe development of hyperglycemia, glucose intolerance and insulin resistance. Reg3β seems to exert two opposite actions in respone to HFD: further diminishing the expression of insulin and Glut2 induced by HFD, while suppressing AMPK activity and increasing p8 expression to compensate for the loss of β-cell function. Taken together, Reg3β is a putative protector that prevents STZ-induced acute damage, but unlikely an islet growth factor and unable to protect β-cells against HFD-induced T2D. The protective effect of Reg3β is likely triggered by acute stress but ineffective against chronic stress induced by HFD.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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 | 0,000 |
| 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) | 0,000 | 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 tête enseignante, 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 ».