1. Significance of dynamic changes in gastric smooth muscle cell apoptosis, PI3K-AKT-mTOR and AMPK-mTOR signaling in a rat model of diabetic gastroparesis.
- Author
-
Zhang MH, Jiang JZ, Cai YL, Piao LH, and Jin Z
- Subjects
- AMP-Activated Protein Kinases metabolism, Animals, Carrier Proteins metabolism, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Experimental metabolism, Disease Models, Animal, Gastroparesis complications, Gastroparesis metabolism, Intracellular Signaling Peptides and Proteins, Male, Myocytes, Smooth Muscle metabolism, Phosphatidylinositol 3-Kinases metabolism, Phosphoproteins metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, Rats, Sprague-Dawley, Ribosomal Protein S6 Kinases, 70-kDa metabolism, TOR Serine-Threonine Kinases metabolism, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins metabolism, Apoptosis, Diabetes Mellitus, Experimental pathology, Gastroparesis pathology, Myocytes, Smooth Muscle pathology, Signal Transduction, Stomach pathology
- Abstract
The aim of the present study was to investigate the significance of cell apoptosis, the phosphoinositide-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway, and the 5' adenosine monophosphate-activated protein kinase (AMPK)‑mTOR pathways in the process of diabetic gastroparesis. Changes in gastric smooth muscle cells of diabetic rats with induced gastroparesis were examined. The diabetic rat model was established by dividing animals into a normal control group and diabetic model groups examined at 2, 4 and 6 weeks. Diabetic gastroparesis was evaluated by examining the rates of gastric residual pigment, whereas flow cytometry was used to detect the apoptosis of gastric smooth muscle cells. The expression levels of PI3K and phosphorylated (p‑) AKT, AMPK, mTOR, tuberous sclerosis complex 2, p70 ribosomal S6 kinase, and eukaryotic translation initiation factor 4‑binding protein 1 were determined in gastric muscles using western blot analysis. Diabetic gastroparesis was confirmed in models at 6 weeks. The apoptosis of gastric smooth muscle cells gradually increased in all diabetic groups, and significant changes were observed in key proteins involved in PI3K‑AKT‑mTOR and AMPK‑mTOR signaling. The results indicated that apoptosis was important in the occurrence of diabetic gastroparesis, and the PI3K‑AKT‑mTOR and AMPK‑mTOR pathways were activated during the apoptotic processes, but were incapable of regulating apoptosis.
- Published
- 2017
- Full Text
- View/download PDF