Translational research : the journal of laboratory and clinical medicine
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The small intestine, which is the area where sugars are absorbed, should be considered in the approaches developed for the treatment of diabetes. However, studies on small intestine damage in diabetic individuals, and the effects of current treatments on the small intestine are very limited. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on small intestine injury in diabetic mice. ⋯ Furthermore, the levels of duodenal tissue glucose, SGLT1, and GLUT2 were decreased, whereas there was an increase in GIP level in diabetic mice administered with exendin-4. Moreover, we determined that the sweet taste receptors T1R2/T1R3, downstream molecules PLCβ2, α-gustducin and associated secondary messengers IP3, cAMP, which were increased in the duodenal tissue of STZ-diabetic mice, decreased with exendin-4 administration. These findings were evaluated as that exendin-4 reduces glucose absorption by suppressing the T1R2/T1R3 sweet taste signal perception pathway in duodenum of STZ diabetic mice.
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ZAK (sterile alpha motif and leucine zipper-containing kinase) is a newly discovered member of the subfamily of mitogen-activated protein kinase kinase kinases (MAP3Ks). The role of ZAK in kidney disease remains largely unknown. In this study, we systematically investigated the expression and function of ZAK in the progression of tubulointerstitial fibrosis (TIF). ⋯ In vivo, intragastric administration of 6p ameliorated TIF and inflammation in UUO and unilateral ischemia-reperfusion injury model. Delayed administration of 6p was also effective in retarding the progression of the established TIF. In conclusion, ZAK is a novel therapeutic target for TIF, and 6p might be a potential therapeutic agent for TIF.
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Sickle cell disease (SCD) is caused by a single point mutation in the β-globin gene of hemoglobin, which produces an altered sickle hemoglobin (HbS). The ability of HbS to polymerize under deoxygenated conditions gives rise to chronic hemolysis, oxidative stress, inflammation, and vaso-occlusion. Herein, we review recent findings using microfluidic technologies that have elucidated mechanisms of oxygen-dependent and -independent induction of HbS polymerization and how these mechanisms elicit the biophysical and inflammatory consequences in SCD pathophysiology. We also discuss how validation and use of microfluidics in SCD provides the opportunity to advance development of numerous therapeutic strategies, including curative gene therapies.