Islet cell transplantation as a cure for insulin dependent diabetes: current improvements in preserving islet cell mass and function

OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of which is lost during the peri-transplantation period. RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in two major directions: preservation of islet cells and tolerance induction. Optimum islet cell viability and function depends on appropriate revascularization of the islet graft and blockade of thrombus formation as well as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation to either upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improve revascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction is currently being best achieved by selecting and combining immunosuppressive agents such as monoclonal antibodies which target the major signaling molecules during immune activation, but which are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developments in effective approaches to protect islets during the peritransplant period. Emerging interest in stem cell biology and differentiation may provide the ultimate solution to the problem of organ scarcity and islet cell protection from the peritransplant induced damage.

Adverse outcomes in type 1 diabetic pregnant women with proliferative diabetic retinopathy

AIM: To report maternal and fetal adverse outcomes, in spite of appropriate treatment and regular follow up, in diabetic pregnant women with proliferative diabetic retinopathy. METHODS: Case series of four young pregnant diabetics aged between 20 and 25 years with type 1 diabetes mellitus and proliferative diabetic retrinopathy. RESULTS: The maternal adverse outcomes were abortion in one patient, pre-eclampsia and preterm delivery in one patient, and renal failure requiring dialysis in one patient. The fetal adverse outcomes were neonatal death in one case and premature baby in another case. CONCLUSION: These cases highlight the fact that diabetic pregnant women should be closely followed up by the obstetricians and physicians when they have proliferative retinopathy. The proliferative diabetic retinopathy should be considered as a part of the assessment when counseling a diabetic woman in antenatal check up and also in the follow up visits during pregnancy.

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb,which depends on migration and integration of newborn neurons from the subventricular zone.In this study,we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus.Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats.Two months after injection,olfactory sensitivity was decreased in diabetic rats.Meanwhile,the number of Brd U-positive and Brd U＋/DCX＋double-labeled cells was lower in the subventricular zone of diabetic rats compared with agematched normal rats.Western blot results revealed downregulated expression of insulin receptorβ,phosphorylated glycogen synthase kinase 3β,and β-catenin in the subventricular zone of diabetic rats.Altogether,these results indicate that diabetes mellitus causes insulin deficiency,which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation,with these changes inhibiting neural stem cell proliferation.Further,these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone.Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Increased PIT1 and PIT2 Expression in Streptozotocin (STZ)-induced Diabetic Mice Contributes to Uptake of iAs^((V))

Objective This study aimed to investigate the susceptibility of mice with streptozotocin（STZ）-induced diabetes mellitus（TIDM） to the uptake of pentavalent inorganic arsenic（iAs^V） and the possible molecular mechanism. Methods TIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na2HAsO4·12H2O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues. Results The concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na2HAsO4·12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAs^V, were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment. Conclusion The increased uptake of iAs^V in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.

Effects of Alloxan-Induced Diabetes on the Expression of Insulin Signal Transmission Molecules

The mRNA of insulin receptor （IR）, the insulin receptor substrates （IRSs）, glucose transporter 2 （GLUT2） and glucokinase （GK） in alloxan-induced diabetic rat livers were amplified by RT-PCR. The protein of the insulin receptor in rat livers was determined by westem-blotting. The results show that IR expression level decreased at the level of mRNA and protein. The gene expressions of IRSs, GLUT2 and GK changed significantly. The hepatic glycogen content in alloxan-diabetic rats treated with insulin （（13.2 ± 0.4） mg·g^-1） did not restore to normal level （（17.0 ±0.4） mg·g^-1） by means of anthrone-H2SO4 methods. The results imply that insulin resistance is developed during inchoate phase of alloxan-induced diabetic rats.