Influence of blood glucose on the expression of glucose transporter proteins 1 and 3 in the brain of diabetic rats

Background The delivery of glucose from the blood to the brain involves its passage across the endothelial cells of the blood-brain barrier （BBB）, which is mediated by the facilitative glucose transporter protein 1 （GLUT1）, end then across the neural cell membranes, which is mediated by GLUT3. This study aimed to evaluate the dynamic influence of hyperglycemia on the expression of these GLUTs by measuring their expression in the brain at different blood glucose levels in e rat model of diabetes. This might help to determine the proper blood glucose threshold level in the treatment of diabetic apoplexy. Methods Diabetes mellitus was induced with streptozotocin （STZ） in 30 rats. The rats were randomly divided into 3 groups： diabetic group without blood glucose control （group DM1）, diabetic rats treated with low dose insulin （group DM2） end diabetic rats treated with high dose insulin （group DM3）. The mRNA end protein levels of GLUT1 end GLUT3 were essayed by reverse trenscriptese-polymerese chain reaction （RT-PCR） end immunohistochemistry, respectively. Results Compared with normal control rats, the G/UT1 mRNA was reduced by 46.08%, 29.80%, 19.22% （P〈0.01） in DM1, DM2, end DM3 group, respectively; end the GLUT3 mRNA was reduced by 75.00%, 46.75%, end 17.89% （P〈0.01） in DM1, DM2, end DM3 group, respectively. The abundance of GLUT1 end GLUT3 proteins had negative correlation with the blood glucose level （P〈0.01）. The density of microvessels in the brain of diabetic rats did not change significantly compared with normal rats. Conclusions Chronic hyperglycemia downreguletes G/UT1 end GLUT3 expression at both mRNA end protein levels in the rat brain, which is not due to the decrease of the density of microvessels. The downreguletion of G/UT1 end GLUT3 expression might be the adaptive reaction of the body to prevent excessive glucose entering the cell that may lead to cell damage.

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

Fanconi-Bickel syndrome in an infant with cytomegalovirus infection: A case report and review of the literature

BACKGROUND Fanconi–Bickel syndrome(FBS)is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene,which encodes glucose transporter protein 2(GLUT2).CASE SUMMARY We report a 7-mo-old girl with cytomegalovirus infection presenting hepatomegaly,jaundice,liver transaminase elevation,fasting hypoglycemia,hyperglycosuria,proteinuria,hypophosphatemia,rickets,and growth retardation.After prescription of ganciclovir,the levels of bilirubin and alanine aminotransferase decreased to normal,while she still had aggravating hepatomegaly and severe hyperglycosuria.Then,whole exome sequencing was conducted and revealed a homozygous c.416delC mutation in exon 4 of SLC2A2 inherited from her parents,which was predicted to change alanine 139 to valine(p.A139Vfs*3),indicating a diagnosis of FBS.During the follow-up,the entire laboratory test returned to normal with extra supplement of vitamin D and corn starch.Her weight increased to normal range at 3 years old without hepatomegaly.However,she still had short stature.Although there was heterogeneity between phenotype and genotype,Chinese children had typical clinical manifestations.No hot spot mutation or association between severity and mutations was found,but nonsense and missense mutations were more common.Data of long-term follow-up were rare,leading to insufficient assessment of the prognosis in Chinese children.CONCLUSION FBS is a rare genetic metabolic disease causing impaired glucose liver homeostasis and proximal renal tubular dysfunction.Results of urine and blood testing suggesting abnormal glucose metabolism could be the clues for FBS in neonates and infants.Genetic sequencing is indispensable for diagnosis.Since the diversity of disease severity,early identification and long-term follow-up could help improve patients’quality of life and decrease mortality.