Zinc content of pancreatic islets in diabetes]

Content and distribution of zinc was studied in the pancreatic islets in human and rabbit diabetes. The diabetes development is followed by a decrease of zinc content in the insulin-producing cells in parallel with the severity of diabetes. The damage to the islet B-cells is the cause of zinc metabolism disturbance in the endocrine pancreas. Influence of high glucose concentration in the blood may be another factor.     

The role of pancreatic islets in experimental pancreatic carcinogenicity.

Our previous studies have suggested that the presence of intact islets is essential for the induction of pancreatic exocrine tumors in the Syrian hamster model. To validate this, we investigated the effect of the carcinogen, N-nitrosobis(2-oxo-propyl)amine (BOP) in hamsters, in which homologous isolated intact islets were transplanted into the submandibular gland (SMG). Freshly isolated pure islets from hamster donors were transplanted into the left SMG of 20 female host hamsters. Ten of these hamsters (group 1) received BOP (40 mg/kg) weekly for 3 weeks. Another 10 hamsters (group 2) were kept untreated. In groups 3 and 4 (10 hamsters each) the salt solution or isolated pancreatic ductal cells, respectively, was injected into the gland. In other groups (10 hamsters each) islets were transplanted into the peri-SMG connective tissue (group 5) or into the renal subcapsular space (group 6). Hamsters of group 1 (40 mg/kg, weekly for 3 weeks) as were group 7 hamsters, which served as BOP-treated controls. All BOP-treated hamsters developed pancreatic lesions. Similar hyperplastic and atypical ductal/ductular proliferation and in situ carcinoma were found in the SMG of many group 1 hamsters. No such lesions were found in the SMG, peri-SMG, or renal subcapsular space of the other groups. Islets appear to be involved in carcinogenicity of BOP. The mechanism is obscure.     

Amyloidosis of the pancreatic islets and diabetes mellitus

Pancreas was examined in 136 patients who died at the age of 7 to 89 years of various diseases including 22 with diabetes mellitus. Amyloidosis of its islands was observed in 9 patients (aged 49 and over); 6 out of them suffered from diabetes mellitus. Number of islands with amyloidosis and amyloid quantity were determined morphometrically. Glucagon-producing A-cells and insulin-producing B-cells in the islands not involved in amyloidosis were counted in sections impregnated by Grimelius. It is found that the development of diabetes is determined not only by the islands amyloidosis but by the quantitative domination of A-cells over B-cells in the islands without amyloidosis as well being the manifestation of aging processes.     

The immune response to islets in experimental diabetes and insulin-dependent diabetes mellitus

Over the past year, a number of important observations have been made in the nonobese diabetic mouse and in clinical insulin-dependent diabetes mellitus concerning the autoimmune response to islets. Assays have advanced to the point where individuals at risk for insulin-dependent diabetes mellitus can be readily identified prior to the onset of symptoms and a number of peptides of proteins expressed by the beta cell have been shown to protect nonobese diabetic mice from developing diabetes. The contributions of CD4⁺ and CD8⁺ T cells to beta cell destruction are beginning to be understood and this information will probably be of value in the design of intervention strategies for use in human subjects.     

Early events in islets and pancreatic lymph nodes in autoimmune diabetes

The specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified islets and pancreatic lymph nodes of 4-week-old NOD mice to NOD-SCID and BALB/c mice. To further characterize the networks implicated in beta-cell destruction, we also performed a time-course analysis using islets and pancreatic lymph nodes of NOD mice from 2 to 25 weeks of age. We found consistent changes by cDNA arrays and RT-PCR analyses among islet genes before the detection of CD3+ T cells in the islet periphery associated with dendritic cell attraction, lymphocyte homing, and apoptosis. In contrast to IL-1, TYNFSF13B and osteopontin genes which were specifically activated, the immunoregulatory cytokine IL-11 was poorly detected in NOD islets and pancreatic lymph nodes. Genes involved in angiogenesis were also specifically activated in NOD islets of 2 and 4 weeks of age. The present time-course macroarray and RT-PCR analyses provides a detailed picture of the different genes involved in autoimmune diabetes and illustrates the importance of islet cell microenvironment that prepares the late beta-cell destruction.     

Type 2 diabetes: Microvascular ischemia of pancreatic islets?

Hyperglycemia is a key factor in both beta cell death and dysfunction as well as in development of microvascular disease. The hypothesis described in this paper suggests that pancreatic microvascular endothelial dysfunction and subsequent microvascular disease of the pancreas causes islet ischemia. This subtle ischemia is the cause of initial dysfunction and subsequent apoptosis of B cells which is preceding development of type 2 diabetes. Moreover, the subtle beta cell ischemia will continue to diminish the beta cells’ ability to secrete the increasing amount of insulin needed as the insulin resistant state progresses into type 2 diabetes. This vicious cycle might perpetuate type 2 diabetes.     

1,6-二磷酸果糖减轻STZ致大鼠胰岛细胞凋亡

目的 探讨1,6-二磷酸果糖（FDP）对链脲佐菌素（STZ）致胰岛细胞凋亡的保护作用与血红素加氧酶/一氧化碳（HO-1/CO）、抗氧化以及NOS/NO系统的关系。 方法 用离体培养乳鼠胰岛细胞,分别检测STZ、FDP作用后细胞形态、细胞活性、细胞凋亡率、细胞HO-1的活性和细胞培养上清液中胰岛素的基础和高糖刺激分泌量以及CO的含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶（GSH-PX）、诱生型一氧化氮合酶（iNOS）和NO的变化。结果：STZ作用后,胰岛细胞活性降低,基础和高糖刺激胰岛素分泌减少,胰岛细胞凋亡率明显增加（p＜0.01）;细胞HO-1活性有所下降,上清液中CO生成减少（p＜0.01）,SOD、GSH-PX活性水平降低、iNOS增多、NO增加。与FDP孵育后细胞活性显著升高,胰岛素基础和高糖分泌量增多,胰岛凋亡率明显降低, HO-1活性和CO生成明显提高（p＜0.01或p＜0.05,同时 SOD、GSH-PX活性水平明显增强、iNOS活性降低、NO生成减少,并且具有剂量依赖性。 结论 FDP能显著改善STZ致胰岛细胞凋亡,其机制可能与增加HO-1/CO系统水平 ,提高抗氧化酶SOD、GSH-PX的活性以及降低iNOS活性,从而减少NO的生成等途径有关。     

Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation

New imaging techniques that couple anatomical resolution to sensitivity may greatly contribute to improving islet transplantation. In the present work, a report is given of the direct detection of islets by magnetic resonance imaging (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A. Experiments on mouse and human islets demonstrated well-tolerated uptake of GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney capsule and xenotransplanted human islets within the mouse liver were detected. Imaging specificity was supported by the absence of signal in unlabeled islet transplants, its persistence upon using fat-suppression MRI protocols and the colocalization with the transplanted islets. In conclusion, direct islet imaging with high spatial and contrast resolution after labeling with GdHPDO3A is demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and intrahepatic human islet xenografts.     

Species specificity of serum factors from rabbits with acute pancreatitis in stimulation of B-cell regeneration in pancreatic islets in experimental diabetes

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, No. 5, pp. 536–537, May, 1993     

Effects of interleukin-15 on suppression of rat pancreatic islets in vitro induced by proinflammatory cytokines

The cytokine IL-15 might contribute to inflammatory processes, but also act as an inhibitor of apoptosis in different cell lines. Furthermore, it has been reported that islet cells express IL-15 after exposure to proinflammatory cytokines, which could indicate a defence reaction. We aimed in this study to investigate if IL-15 could influence cell death and/or functional impairment of rat pancreatic islets induced by in vitro exposure to a combination of cytokines (25 U/ml IL-1beta+1000 U/ml IFN-gamma+1000 U/ml TNF-alpha). The effect of IL-15 itself on the function of rat pancreatic islets was also studied. Isolated rat islets were exposed for 24 h to IL-15 at different concentrations in the presence or absence of the cytokine mixture. The cytokines caused a strong inhibition of glucose-stimulated insulin release and the glucose oxidation rates. IL-15 (0.1-10 ng/ml) could not prevent the functional suppression caused by these effects. The cytokine combination caused a decline in whole islet DNA content and a marked increase in non-viable cells analysed by propidium iodide (PI) and annexin V staining. However, there was no significant decrease in whole islet DNA content when IL-15 (0.1 or 1.0 ng/ml) was present together with the cytokine mixture. On the other hand, IL-15 failed to influence the increase in cell death after PI and annexin V staining. If anything, IL-15 alone had a slight stimulatory effect (glucose oxidation rate) on islet cells. In conclusion, we can not exclude that IL-15 might antagonize some cytokine mediated cell death in islet cells, however, IL-15 fails to counteract functional suppression induced by cytokines.     

Oxidation of [1,12-14C]dodecanedioic acid by rat pancreatic islets

Several aliphatic dioic acids were recently reported to stimulate insulin release in isolated rat pancreatic islets incubated at close-to-physiological D-glucose concentrations. In order to gain insight into the mode of action of these acids in pancreatic islet B-cells, the oxidation of [1,12-14C]dodecanedioic acid (5.0 mM) was now measured in rat islets. Expressed as pmol of [1, 12-14C]dodecanedioic acid equivalent, the production of 14CO2 was close to 1.0 pmol/islet per 120 min, representing about 8% of that attributable to the oxidation of D-[U-14C]-glucose (8.3 mM). The dioic acid and the hexose failed to exert any significant reciprocal effect upon their respective oxidation rate. These findings support the view that the insulinotropic action of dodecanedioic acid, and presumably other aliphatic dioic acids, is causally linked to their capacity to act as nutrients in pancreatic islet cells.