Cell direct reprogramming：a new technique for treating diabetes

Diabetes is characterized by an absolute or relative deficiency in β-cell mass, which cannot be reversed with existing therapeutic strategies. The restoration of the endogenous islet β-cells can stabilize the level of blood glucose. The islet β-cells can be obtained from the directional differentiation of stem cells, but the process is complex and has the risk of teratomas generation. Cell direct reprogramming, one terminal differentiated cell can transdifferentiate into another kind of terminal differentiated cell, which is other than directional differentiation from stem cells. Direct reprogramming gives rise to the generation of islet β-cells from one terminal differentiated cell, may be preferable for diabetes therapy because of its unique advantage.     

Ultrastructural impairment of islet microvascular endothelial cells in STZ-induced type 1 diabetic mice

AIM: To investigate the ultrastructural changes of islet microvascular endothelial cells in STZ-induced type 1 diabetic mice. METHODS: BALB/c mice were randomly divided into diabetic group and control group. The expression of insulin and platelet-endothelial cell adhesion molecule-1 (CD31) in islet microvessels was detected by immunohistochemical staining. The ultrastructural changes of islet β cells and islet microvessels were observed under transmission electron microscope. RESULTS: Compared with control group, the number of islet β cells, ratio of β cells/α cells, average number of secretory granules in β cells and insulin expression area per islet in diabetic group were significantly decreased (P<0.01). Besides, diabetic group had fewer microvessels with lower expression of CD31 (P<0.01). Mitochondria in islet microvascular endothelial cells and pericytes in diabetic group were swelling. The basement membrane of islet microvessels became thicker in diabetic group (P<0.01). CONCLUSION: Islet microvascular endothelial cells were impaired in type 1 diabetic mice.     

转录因子Islet1与心脏发育

结合鸡胚心脏发育的过程,就Islet1与心脏发育之间的关系作一综述,以期为Islet 1基因研究提供参考。     

Cellular and Molecular Characterization of a Feline Insulinoma

Background: Insulinoma is an autonomous insulin-secreting islet cell neoplasm that is rarely diagnosed in cats. The clinical and pathological aspects of feline insulinoma have been described previously, but the molecular characteristics of these tumors have not been investigated.
Objectives: The study objectives were to characterize peptide hormone production and determine expression of selected genes involved in glucose metabolism and insulin secretion in a feline insulinoma.
Methods: Immunohistochemistry and RT-PCR were used to examine hormone and gene expression, respectively, by insulinoma cells.
Results: Immunohistochemistry examination indicated that the tumor cells expressed insulin, chromogranin A, and somatostatin but not glucagon or pancreatic polypeptide. The tumor expressed several genes characteristic of pancreatic beta cells (β cells) including insulin ( INS ), glucose transporter 2 ( GLUT2 ), and glucokinase ( GCK ). The tumor also expressed hexokinase 1 ( HK1 ), a glycolytic enzyme not normally expressed in β cells. GCK expression was higher in the insulinoma than in normal pancreas from the same cat. The GCK  :  HK1 ratio was >20-fold higher in insulinoma tissue than in normal pancreas.
Conclusions and Clinical Importance: The feline insulinoma produced several peptide hormones and expressed genes consistent with a β-cell phenotype. The pattern of hexokinase gene expression in tumor cells differed from that of normal pancreas. These findings suggest insulinoma cells may have an increased sensitivity to glucose that could contribute to the abnormal insulin secretory response observed at low serum glucose concentrations.     

Advance in islet β cell development and regeneration

Islet β cells excrete insulin and play a crucial role in glucose homeostasis. Decreased β cell mass or/and β cell dysfunction are one of the fundamental characteristics of diabetes. The advance in understanding β cell development and regeneration provides new approaches to diabetes treatment. This review focuses on the molecular mechanism about β cell development and the sources for β cell regeneration.     

Effects of fructose sodium diphosphate on expression of CHOP and JNK in endoplasmic reticulum stress and islet apoptosis in rats with type 2 diabetes

AIM: To study the effects of fructose sodium diphosphate (FDP) on the expression of CHOP and c-Jun N-terminal binase(JNK) in endoplasmic reticulum stress and islet apoptosis in the rats with type 2 diabetes mellitus (T2DM). METHODS: T2DM model was established in male Wistar rats by feeding of high lipid diet and injection of streptozotocin. The rats were divided into 4 groups (n=8):normal control group, T2DM model group, T2DM+low-dose FDP (2 mL穔g^-1穌^-1, ip) group and T2DM+high-dose FDP (5 mL穔g^-1穌^-1, ip) group. The rats in the treatment groups received FDP for 8 weeks. The levels of fasting blood glucose (FBG), fasting serum insulin (FINS) and insulin sensitivity index (ISI) were measured. TUNEL was used to detect the islet apoptosis. The protein levels of CHOP and JNK were determined by the method of immunohistochemistry. RESULTS: (1) Compared with normal control group, FBG, FINS, the expression of CHOP and JNK, and apoptosis in T2DM model group were significantly increased (P<0.01). The level of ISI was significantly decreased. (2) Compared with T2DM model group, the levels of FBG and FINS, the expression of CHOP and JNK, and apoptosis in high-dose FDP group were significantly decreased. The level of ISI was significantly increased (P<0.01). However, the level of FBG, the expression of CHOP and JNK, and apoptosis in low-dose FDP group were significantly decreased. Compared with low-dose FDP group, the levels of FBG and FINS, the expression of CHOP and JNK, and apoptosis in high-dose FDP group were significantly decreased. The level of ISI was significantly increased (P<0.01 or P<0.05). CONCLUSION: FDP may prevent islet cells from apoptosis in T2DM rats by decreasing the expression of CHOP and JNK.     

桑叶多糖MLPⅡ的基本结构及对糖尿病模型大鼠的降血糖作用

从桑叶中分离纯化获得一种具有降血糖活性的均一多糖组分MLPⅡ。高效液相色谱分析桑叶多糖MLPⅡ主要由甘露糖(man)、鼠李糖(rha)、葡萄糖(glc)、木糖(xyl)和阿拉伯糖(ara)等5种单糖组成,其摩尔比为n(man)∶n(rha)∶n(glc)∶n(xyl)∶n(ara)=8.73∶1.04∶6.53∶2.13∶1.00;红外光谱显示桑叶多糖MLPⅡ的主要连接键为β-糖苷键。桑叶多糖MLPⅡ对糖尿病模型大鼠的降血糖试验结果表明,150 mg/kg MLPⅡ治疗组糖尿病模型大鼠的体质量与对照组糖尿病模型大鼠相比提高了26.22%,而空腹血糖(FBG)浓度降低了52.89%,达到极显著水平,并且治疗组糖尿病模型大鼠的糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)和C-肽(C-P)水平得到改善,损伤胰岛细胞得到修复,胰岛β细胞合成和胰岛素分泌的能力增强。研究结果提示,桑叶多糖MLPⅡ可有效控制糖尿病模型大鼠的体质量和空腹血糖水平,并改善糖耐量,而促进糖尿病模型大鼠胰岛β细胞合成及胰岛素分泌可能是桑叶多糖MLPⅡ降血糖作用机制之一。     

胰岛淀粉样多肽的研究进展

胰岛淀粉样多肽(islet amyloid polypeptide，IAPP)是一种有关调节糖代谢的新激素。为探讨胃肠胰IAPP免疫反应细胞的形态分布，深入了解IAPP的生理作用及疾病状态下的改变，特对其研究进展作一综述。     

胎猪胰岛源胰腺干细胞分离培养与诱导分化试验

 【目的】分离培养胎猪胰腺干细胞对其进行功能检测。【方法】用先悬浮后贴壁的方法从胎猪胰岛获得胰腺干细胞，用免疫组化方法鉴定该细胞，以MTT法测定其不同代次的生长活性，诱导该细胞成为胰腺内分泌细胞并检测其功能。【结果】分离得到的细胞不表达nestin，而表达导管上皮细胞标志ck-19、平滑肌标志α-actin,其在体外的生长行为有类似胚胎干细胞样生长形态，细胞体外增殖活力很强，现已传至18代，细胞经诱导后分化为分泌胰岛素的胰腺内分泌细胞，并且伴随着细胞超微结构的改变。【结论】通过本方法可以分离到胎猪胰腺干/祖细胞，经诱导分化可形成有功能的胰岛样细胞团并释放胰岛素。