Objective To investigate the ultrastructure changes of pancreatic islets alpha cells in rats with impaired glucose tolerance.Methods 16 Wistar rats were randomly assigned into normal glucose tolerance group(NGT group,n =8)and impaired glucose tolerance group(IGT group,n =8).NGT group were fed with routine diet and IGT-group were fed with high-sugar high-fat diet.At the 12th week,IGT models were considered successful if the level of 2-hour peripheral blood glucose(2 h PG)was between 7.8 and 11.1 mmol/L in oral glucose tolerance test and continued for more than a week.The pancreas tail of animals in the NGT group and IGT group rats was removed for ultrastructure observation.Alpha cells were observed under transmission electron microscope.Results The big-plump secretory granule with aureole appeared in pancreatic islets alpha cells of NGT group,and it contained a round dense core.The nuclear chromatin and contents were evenly distributed.Mitochondria and en-doplasmic reticulum arranged tightly and orderly.Compared with NGT group,the quantities of secretory granule increased significantly in IGT group.The gap between dense core and membrane was narrower.The quantities of mitochondria and rough endoplasmic reticulum increased significantly.There was no significant change for the structure of the other cell organelle.Conclusion The pathogenesis of IGT is associated with ultrastructural changes and dysfunction of pancreas islets alpha cells.

Objective To investigate the effect of glucagon-like peptide-1 agonist (exendin-4) on expression of glucose transporter 4 (GLUT4) in the skeletal muscle of rats with impaired glucose tolerance (IGT).Methodis 54 Wistar rats were randomly assigned into normal glucose tolerance group (NGT group,n =18) and impaired glucose tolerance group(IGT group,n =36).The rats in NGT group were fed with routine diet and the rats in IGT group were fed with high-sugar high-fat diet.At the 12th week,IGT models were tested successful.Then,half of the rats were allocated to intervention group (Ex group) and the rest were set as IGT control group.The rats in Ex group were subject to exendin-4 subcutaneous injection (5 μg/kg,twice daily).Each rat in NGT group and IGT control group was given the same volume of saline as injection.FBG and 2 h BG were measured before intervention and after 4 weeks.The expression of GLUT4 mRNA and GLUT4 in the skeletal muscle were respectively measured by real time quantitative polymerase chain reaction and immunohistochemistry.Inter-group comparison was conducted using analysis of variance (ANOVA) and least square deviation-test (LSD-t).Results Before intervention,compared with NGT-group,the 2 h BG in IGT control group and Ex group were higher,the GLUT4 mRNA of skeletal muscle in IGT control group and Ex group were lower (respectively P ＜ 0.05).The skeletal muscle cells in IGT control group and Ex group were less colored while the skeletal muscle cells in NGT group were colored extensively,and more colored granules.After 4 weeks of exendin-4 intervention,compared with IGT control group and Ex group of non-intervention,the 2 h BG level in Ex group was lower and the expression level of GLUT4 mRNA of skeletal muscle was higher (respectively P ＜ 0.05).After intervened with exendin-4 for 4 weeks,the GLU protein mainly expressed in cytoplasma of skeletal muscle cells.Its expression was higher in Ex group than in IGT group and in Ex group before intervention.Conclusion Exendin-4 may up-regulate the expression of GLUT4,increase glucose intake of the skeletal muscle,and reduce postprandial blood sugar.

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells