糖尿病大鼠胰岛中激素敏感性脂肪酶表达和活性的变化

观察糖尿病大鼠胰岛中激素敏感性脂肪酶(HSL)和甘油三酯(TG)的变化,发现高脂饮食的糖尿病大鼠胰岛内脂质含量、HSL的表达和活性明显高于正常对照组(均P＜0．05),降低血糖不仅减少胰岛中TC的含量,而且HSL的表达和活性也下降。     

微囊胰岛移植对实验性糖尿病大鼠脂质过氧化物水平的影响

目的观察微囊化胰岛移植对实验性糖尿病大鼠脂质过氧化物水平的影响。方法设立正常对照组、模型组和移植组。移植组接受激囊化胰岛移植。结果移植组血糖降至711±1．28mmol／L．SOD活力为547．7±55．28μg／g．Hb，MDA含量为4．31±0．41μmol／L，模型组血糖仍大于16．67mmol／L以上，SOD活力为420±42．88μg／g．Hb，MDA水平为5.33±1．4μmol／L，两组相比有显著性差异（P＜0．01）。结论提示微囊保护异种移植胰岛免受排斥，使胰岛在受体内长期生存，受血糖调控释放胰岛素起治疗作用，而且也能减少自由基对组织的损伤，纠正受体的精代谢紊乱。     

糖尿病胰岛移植及细胞治疗的细胞来源

胰岛移植或细胞治疗是根治1型糖尿病较为理想的方法，但同时也面临着供体匮乏的难题。近年来研究显示，除同种自体或异体胰岛外，异种胰岛尤其是选择猪供胰成为众多学者关注的焦点；另外对扩增胰腺β细胞及制造胰岛素分泌细胞株的研究亦取得了一定的成果；而干细胞工程及转基因技术的应用，使利用干细胞治疗糖尿病及人工构建类胰岛细胞成为可能。     

激素敏感性脂肪酶研究新进展

激素敏感性脂肪酶(HSL)是脂肪分解的限速酶．能水解甘油三酯(TG)、甘油二酯(PG)、甘油一酯、胆固醇酯和其他脂质及水溶性底物，产生甘油和脂肪酸。它主要存在于脂肪组织。最近研究发现在胰腺、睾丸、肌肉、肾上腺等组织中也有表达，而且可能发挥更独特的作用；还发现HSL的活性和基因的改变可能与代谢紊乱相关。     

胰岛细胞抗体阳性的老年糖尿病患者B细胞功能的变化

一、资料与方法１．对象：老年２型糖尿病患者（ＤＭ２组）８０例,均为我院１９９７年１月至１９９８年２月收治的住院或门诊患者。男５２例,女２８例,年龄６０～７１岁,平均（６３．９±４．８）岁。病程３个月至２４年,单纯饮食和（或）口服降糖药控制血糖,均未用...     

链脲佐菌素所致糖尿病大鼠骨髓中存在胰岛样细胞

本研究证实糖尿病大鼠骨髓中存在表达胰岛素、C肽、胰高血糖素、生长抑素和胰淀粉样多肽的细胞簇，并检测到胰岛发育和功能相关基因的表达，这些胰岛样细胞可能是骨髓中的成体干细胞转分化而来。     

老年糖尿病患者胰岛细胞自身免疫现象

目的：了解老年糖尿病患者胰岛细胞抗体（ICA）及谷氨酸脱羧酶抗体（GADA）的检出情况及其胰岛β-细胞功能状况。方法：87例新发的老年糖尿病患者为实验组,100例新发非老年糖尿病病人为对照组。2组均行ICA、GADA检测、口服葡萄糖耐量实验及C－肽释放实验。结果：实验组中有14．9％呈ICA和（或）GADA阳性,对照组中有16％呈上述抗体阳性,2组阳性率无明显差异（P＞0．05）。与其他组相比,抗体阳性的老年糖尿病患者服糖前后各点血清C－肽浓度均较低（P＜0．01）。结论老年糖尿病中亦有一定数量的1型糖尿病患者,其发生率与非老年组相同,但这类患者胰岛细胞储备能力减退更为明显。     

The pancreatic islets in diabetes

Despite the fact that heterogeneity of diabetes in man has become more and more evident in recent years, its pancreatic pathology is still represented by two distinct entities, roughly corresponding to the classic juvenile-onset and maturity-onset types of the disease.In juvenile-onset, insulin-dependent diabetes, the pancreatic islets show severe and pathognomonic changes. B cells are greatly reduced in number already at clinical onset. Contrary to classic opinion they do not always disappear in the years to follow. Insulin's, a common finding in the pancreas of recent onset juvenile diabetic subjects, is compatible with a viral infection as well as with an autoimmune reaction as the cause of B cell destruction. In the pancreas of juvenile-onset diabetic subjects the islets, which in the past have been regarded as atrophic and inactive, are actually composed of cells containing glucagon and somatostatin. There is also a profound distortion of islet organization, and many endocrine cells are scattered as single cells in the exocrine tissue. These findings may well account for the abnormal secretory behavior of the glucagon-secreting A cells in insulin-dependent juvenile-onset diabetes.In maturity-onset, noninsulin-dependent diabetes, the pancreatic pathology is extremely variable and not pathognomonic. A numeric reduction of the B cells can be demonstrated in many maturity-onset diabetic subjects, but this reduction is much more moderate than in insulin-dependent juvenile-onset diabetic subjects and does not account for the disease. The same amount of B cell reduction can be found in many elderly subjects without clinical evidence of diabetes. In many maturity-onset diabetic subjects, the cytologic characteristics of the B cells suggest a decreased responsiveness to the stimulus of hyperglycemia. Islet fibrosis and hyalinosis (amyloidosis), although common, cannot explain this secretory dysfunction. The exact site of the defect in the B cells of maturity-onset diabetic subjects remains to be defined. Further investigations are necessary to assess the role of disturbed intraislet intercellular relationships in the pathogenesis of late-onset diabetes.The dual pattern of islet pathology in diabetes in man does not preclude a more profound heterogeneity in the etiology and pathogenesis of the disease.     

Structural changes of pancreatic islets in genetically obese rats

Summary Light and electron microscopic observations were performed on pancreatic islets from genetically obese rats, (Zucker, fatty), from 5 to 52 weeks of age. At 5 weeks of age, islets were moderately hypertrophied. After that age, hypertrophy of islets became more prominent, until 24 weeks of age, with accompanying degranulation of B cells. The plasma insulin level also continued to increase during this period, but the glucose level was normal. Degranulated B cells contained a highly developed Golgi complex, numerous vesiculated, granular, endoplasmic reticulum and a small number of secretory granules, but no glycogen deposits. Emiocytosis and microtubule formation were very remarkable with these B cells. Frequently, mixed or intermediate cells, such as exocrine-endocrine or ductural-endocrine cell, were observed in pancreas with hypertrophied islets. At 52 weeks of age, both the plasma insulin and triglyceride levels decreased. In the pancreas, there were observed proliferation of fibrous tissue and well granulated B cells in hypertrophied islets. Hence, in fatty rats, pancreatic islets were in an active state during the period of development of obesity and hyperlipaemia (from 5 to 24 weeks of age). These correlates of obesity and hyperinsulinism disappeared at 52 weeks of age.     

Sequential morphological changes in pancreatic islets of spontaneously diabetic rats

This study describes the sequential morphological changes in pancreatic islets from 1-, 6-, and 18-month-old male eSS rats, as compared to aged-matched control animals. Spontaneous diabetes mellitus was confirmed in 6- and 18-month-old eSS rats after an oral glucose tolerance test. Light microscopic immunocytochemical and morphometric techniques were used to study islet-cell populations. The pancreas was normal, and the morphometric methods did not reveal significant changes in islets from 1-month-old rats. However, 6-month-old eSS animals showed disruption of islet architecture and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were increased, whereas the Vvi of exocrine tissue and the Vvi and percentage of A cells were diminished. Eighteen-month-old eSS rats also exhibited conspicuous islet lesions. Nevertheless, the Vvi of endocrine tissue and the Vvi and percentage of B cells were diminished, while the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. Our results provide further quantitative evidence for the sequential morphological events occurring in the pancreatic islets of a useful animal model of diabetes mellitus.     

Histopathology and immunohistochemistry of pancreatic islets in fibrocalculous pancreatic diabetes

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.     

Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats.

Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin-dependent diabetes mellitus), have only been studied in male rats and in 18-weeks old rats or younger. In this study, we have examined in both male and female ZDF rats the histopathological changes longitudinally, from 6 to 32 weeks of age. We studied islet architecture and cellular distribution of the various islet hormones both in ZDF and control rats. In the ZDF rats, aging was initially associated with an enlargement of the islets. From 18 weeks onwards, no further enlargement was noted but islet boundaries became increasingly irregular, leading to the appearance of projections of endocrine cells into the surrounding exocrine tissue. At the islet boundaries as well as within the islets progressive fibrosis was observed with increasing amounts of collagen and reticular fibers. In the islets, staining intensity of both insulin and islet amyloid polypeptide (IAPP) increased slightly till 10 weeks of age and thereafter decreased rapidly. In contrast, the staining intensities of glucagon, somatostatin, and pancreatic polypeptide (PP) did not change. Even at the age of 32 weeks, just the beta-cells and not the other endocrine islet cells appear to be affected. In control rats, aging evoked only minor changes. Thus, we observed that during prolonged development of diabetes mellitus in both male and female ZDF rats histopathological changes in the pancreatic islets became progressively more severe, eventually leading to disintegration of the islets.     

The effects of cyproheptadine on glucose tolerance and pancreatic islets in rats

Summary The effects of cyproheptadine (CPH) on plasma levels, of glucose, insulin and glucagon were studied in rats in order to clarify the diabetogenicity of this compound. CPH was given to the rats at a daily dose of 45 mg per kg body weight via gastric intubation for up to 20 days. Glucose intolerance appeared after 5 days of CPH treatment without significant increase in fasting glucose level. Plasma insulin response to glucose loading was depressed in the early phase of the glucose tolerance test in groups treated for 10 and 20 days. In these groups the insulinogenic index was significantly lowered. Pancreatic insulin content decreased rapidly after single dose of CPH. Plasma level and pancreatic content of glucagon were not changed by this compound. These results suggested that chronic treatment with CPH caused glucose intolerance in rats through its direct influence on pancreatic B-cell function.     

Prolactin-induced changes in protein expression in human pancreatic islets

Ex vivo islet cell culture prior to transplantation appears as an attractive alternative for treatment of type 1 diabetes. Previous results from our laboratory have demonstrated beneficial effects of human prolactin (rhPRL) treatment on human islet primary cultures. In order to probe into the molecular events involved in the intracellular action of rhPRL in these cells, we set out to identify proteins with altered expression levels upon rhPRL cell treatment, using two-dimensional (2D) gel electrophoresis and mass spectrometry (MS). An average of 300 different protein spots were detected, 14 of which were modified upon rhPRL treatment (p<0.01), of which 12 were successfully identified using MS and grouped according to their biological functions. In conclusion, our study provides, for the first time, information about proteins that could be critically involved in PRL's action on human pancreatic islets, and facilitate identification of new and specific targets involved in islet cell function and proliferation.     

Imaging inflammation of the pancreatic islets in type 1 diabetes

Type 1 diabetes is the clinical manifestation of aberrant leukocytic infiltration of the pancreatic islets; it is usually diagnosed only very late in disease progression, after the critical autoimmune phenomena have mostly played out. A noninvasive means of directly monitoring the evolution of islet infiltrates would have important research and clinical applications. We have exploited fluorescence and MRI of long-circulating magnetofluorescent nanoparticles to visualize micro-vascular leakage, as an indicator of inflammation, in pancreata of mouse models of type 1 diabetes ex vivo or in vivo. We could detect the onset and evolution of insulitis in vivo and in real time, permitting us to study the natural history of diabetes in individual animals.