The frequency distribution of the number and volume of the islets Langerhans in man. I. Studies on non-diabetic adults.
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Humans↗
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Two cases of persistent hyperinsulinemic hypoglycemia that showed spontaneous regression and maturation of the Langerhans islets.
Near-total pancreatectomy has been recommended as the treatment for persistent hyperinsulinemic hypoglycemia (PHH) in infants. However, recently there has been a report described that one third of 95% pancreatectomy failed to prevent hypoglycemia and more than two thirds had diabetes ultimately. The authors experienced 2 cases of PHH, which raise a query about the extensive pancreatectomy. Case 1: A female patient who manifested PHH shortly after birth underwent less extensive pancreatectomy twice at age 2 months and 8 years. After each operation, her clinical symptoms regressed, and she became free from the disease eventually. Histologic findings showed nesidioblastosis in which the islets clearly matured. Case 2: A male infant with PHH had an absolute indication for pancreatectomy. However, after a meticulous control of the blood glucose level with parenteral nutrition followed by continuous enteral nutrition feeding combined with medication, he became free from the disease. The current cases show there exist cases of PHH in which the islets mature and symptoms regress spontaneously. Therefore, we conclude near-total pancreatectomy is not always the treatment of choice. As an alternate strategy, long-term controlled feeding and medication combined with or without less extensive pancreatectomy should be considered with the expectation of spontaneous regression.
Adenoma, Islet Cell↗
Polyamide 4,6 membranes for the encapsulation of Langerhans islets: preparation, physico-chemical properties and biocompatibility studies.
Porous polyamide 4,6 membranes developed as semi-permeable and biocompatible membranes for the encapsulation of pancreatic islets were prepared by precipitation in water. Different membrane morphologies were obtained by varying the molecular weight of polyamide 4,6, the solvent evaporation time and the composition of the casting solution. Each membrane was submitted to differential scanning calorimetry and water flux measurements to study the total water content and the different kinds of water in correlation with its permeability performances. Their biocompatibility was first evaluated by a surface protein adsorption test. Of the various membranes, the one prepared by immersion in water after 5 minutes of solvent evaporation, of 15% KS200 polyamide 4,6 solution added with 1% of polyvinylpyrrolidone K30 seems to be the most promising. This membrane is characterized by a low adsorption of proteins, a high hydraulic coefficient and an asymmetric structure. Such a membrane represents a good candidate to be an efficient immunological barrier. It also exhibits good glucose and insulin diffusion properties. Moreover, rat islets cultivated on its surface were not affected by its presence and no important cell adhesion was noticed when implanted in mice. This membrane exhibits most of the properties suitable for the islet encapsulation with a view to developing a bioartificial pancreas.
Journal Article↗
Experimental hypoglycemizing tumor of B-cells of Langerhans islets produced by the combined action of streptozotocin annd nicotinamide in the rat.
Young male and female Wistar-Velaz rats were treated with streptozotocin-nicotinamide combination according to the method of Rakieten and examined periodically for 23 months for fasting and postprandial glycemia, by intravenous, intraperitoneal or intragastric glucose tolerance and tolbutamide tests with the aim to detect in vivo the experimentally produced nesidiomas. One male rat with severe hypoglycemia, apparent first on tolbutamide test after twelve months, later also on glucose tolerance test and fasting hypoglycemia associated with paraplegia with macroscopically and microscopically documented nesidioma is described. The exstirpation of this nesidioma was followed first by normalization and later by development of latent diabetes.
Adenoma, Islet Cell↗
[Apropos of a series of 20 adenomas of Langerhans islets].
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Adenoma, Islet Cell↗
[Localizing of Langerhans islets adenoma by transhepatic portal catheterization].
BACKGROUND: The procedures used to locate pancreatic endocrine tumors have only limited success in infants and children in whom the nodules may be small. Portal catheterization may therefore be useful. CASE REPORT: A child aged 6 yrs 4 months was admitted because of several recent episodes of pallor and sweating associated with hypoglycemia. Further investigation showed moderate hyperinsulinemia and low blood levels of ketone bodies and branched amino-acids after a 15 hr fast. Celiac angiography was normal. The hypoglycemic episodes recurred despite treatment with diazoxide for 6 months. A transparietal portal catheterization was therefore performed. Selective pancreatic venous sampling showed high concentrations of insulin in two small veins draining one part of the head of the pancreas (117 and 89 microU/ml). The head of pancreas was removed 16 months later. Extemporaneous examination revealed an adenoma 0.8 cm in diameter. This patient has completely recovered, 8 months after surgery. CONCLUSION: Transparietal portal catheterization can detect pancreatic areas with high insulin secretion. It may also help the interpretation of celiac angiographs in children, as diagnosis may be obscured by the normal rich vascularity of the pancreas in these patients.
Adenoma, Islet Cell↗
Observations on the intrinsic innervation of the islet of Langerhans of Rattus rattus rufescens (Indian black rat).
The innervation of Langerhans' islets appeared rather profuse. Generally the nerve fibres of the peri-insular plexus formed a basket enveloping the islet of Langerhans. The peri-insular ganglia were occasionally seen. No autonomic interstitial cells of Cajal nor nerve endings were observed in the islet of Langerhans, due to the thickness of the sections. The 'complexes sympathico-neuro-insulaires' were occasionally seen. The plexuses and neural terminal network were seen connected to each other; thus they are not separate entities.
Animals↗
[Ultrastructural modifications in the pigeon islets of Langerhans after epiphysectomy and treatment with epifizan (author's transl)].
The endocrine pancreas in pigeon consists of three types of Langerhans' islets (light, dark and mixed) each one having D, A and B cells in different proportions, representing 42%, 32% and 25%, respectively, from the total amount of endocrine pancreas. The D-cells are electrondense and contain many large spheric secretory granules (300...500 nm) with an adherent membrane to its content. The A-cells are spheric or columnal in shape, having few cell-organelles, a low electron density and contain spheric or oval secretory granules (200...400 nm) with a narrow space between the membrane and its content. The B-cells are elongated, electrondense, have many cell-organelles and contain many polymorph secretory granules (180...260 nm) which have in their majority a crystalline content which is separated from the membrane by a halo. After epiphysectomy the A (glucagon-secreting) and B (insulin-secreting) cells appear to be stimulated: the nuclei are enlarged, the synthesis processes are accelerated and the secretory granules increased. The stimulation of the glucagon synthesis is the consequence of the hypoglycaemia, caused by pinealectomy. The D (somatostatin-secreting) cells appear to be inhibited, having decreased secretory granules and modifications of some cell-organelles. This seems to be connected only with hypertrophy of the B-cells. After epiphysectomy followed by a treatment with Epizifan, the A-cells appear to be exhausted, caused by a persistent secretory activity, these cells containing only a small quantity of immature secretory granules. The B-cells are overloaded with secretory granules, having some damaged cell-organelles and appear to be inhibited in the releasing of their secretory granules. The D-cells are very active, rich in secretory granules, allowing the conclusion that an active synthesis and secretion have been taking place. These facts could be explained only by an inner regulation mechanism of the Langerhan's islet which is disturbed by pinealectomy but not restored by the nonspecific (cattle) Epifizan.
Animals↗
Inflammatory mediators expressed in human islets of Langerhans: implications for islet transplantation.
Expression of immune modulating mediators in human Islets of Langerhans could have important implications for development of autoimmunity in type 1 diabetes and influence the outcome of clinical islet transplantation. Islets obtained from five donors were analyzed at various times after isolation using cDNA array technology. The Atlas Human Cytokine/Receptor and Hematology/Immunology nylon membranes representing 268 genes and 406, respectively, were used and the relative expression of each gene analyzed. Of the 51 gene products identified, high mRNA expression of MCP-1, MIF, VEGF, and thymosin beta-10 was detected in all islet samples. IL-8, IL-1-beta, IL-5R, and INF-gamma antagonist were expressed in islets cultured for 2 days. IL-2R was expressed in islets cultured for more than 6 days. In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation.
Cells, Cultured↗
Effects of dental materials on insulin release from isolated islets of Langerhans.
OBJECTIVES: To investigate the possibility of using a whole organ model for evaluating the biological effects of dental restoration materials in vitro. METHODS: The effect on insulin release of isolated Langerhans islets of a series of dental materials was examined. The islets were incubated for 1h with extracts obtained from various dental materials and insulin was assayed radioimmunologically with crystalline mouse insulin. The results were analysed statistically using analysis of variance (ANOVA) and Scheffe's test at a significance level of p < 0.05. RESULTS: One dental ceramic, Vita VMK 95, significantly (p < 0.01) decreased the insulin release, whereas another dental ceramic, Empress (p < 0.01), a partly re-cast high-noble gold alloy (p < 0.001), a modified high-noble gold alloy (p < 0,05), and unalloyed copper (p < 0.001) significantly increased the release of insulin. SIGNIFICANCE: The results demonstrate a new instance of examining the biological effects of dental restoration materials. The method provides information about the effect of different materials on organ level in vitro that can complement other in vitro tests.
Aluminum Oxide↗
Induction of insulin secretion by a component of Urtica dioica leave extract in perifused Islets of Langerhans and its in vivo effects in normal and streptozotocin diabetic rats.
The blood glucose lowering effect of Urtica dioica (Stinging Nettle) as a medicinal plant has been noted in old writings such as those of Avicenna. Recently, there has also been other investigators that indicated the hypoglycemic effect of Urtica dioica. But so far, the mechanism of this effect has not been deduced. In this report, a perifusion system is arranged in which an exact number of Langerhans Islets were exposed to several fractions of extracts of Urtica dioica by TLC. The active ingredient fraction named F(1), caused a marked increase in insulin secretion. A simultaneous assay of glucose showed that the increase in insulin level was associated with a decrease in glucose level. Furthermore, the active component of Urtica dioica was found to increase the insulin content of blood sera in normal and streptozotocin diabetic rats that were injected intraperitoneally (i.p.) with the active ingredient of the extract. The in vivo studies presented in this report show that not only an increase in insulin level of blood sera was observed in rats after 30 min from the initial point of injection but a simultaneous decrease of blood sugar was detected when similar sera was tested for glucose. The increase in insulin level was six times during the 120 min of our determination. The decrease in blood sugar was found to be similar both in the level and time of initiation. On the basis of our findings, we assume that F(1) is the active ingredient of plant leaves extract. The results show that the blood lowering effect of the extract was due to the enhancement of insulin secretion by Langerhance Isletes.
Animals↗
Morphological and functional changes of islets of Langerhans in FK506-treated rats.
FK506, a new immunosuppressant, caused glucose intolerance in rats given daily oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia under normal feeding. Besides the glucose intolerance, insulin secretion was impaired and insulin levels in the pancreas were lowered. Histopathologically, there was vacuolation of the Langerhans islets in the animals given 10 mg/kg. After withdrawal of the drug, these changes in pancreatic function and morphology returned to normal within 2 weeks. The findings indicate that FK506 caused dose-dependent but reversible islet toxicity in rats.
Animals↗
Apoptosis in cultured rat islets of langerhans and occurrence of Bcl-2, Bak, Bax, Fas and Fas ligand.
Isolated Langerhans islets are widely used for diabetic transplantation experiments and investigations of the mechanisms leading to the death or survival of insulin-producing cells in cultured islets. The present study was aimed at investigating programmed cell death and the role of apoptosis-associated peptides in insulin and glucagon cells of islets isolated from untreated rats and held in cultured suspension. Islets were removed from medium on days 0, 7, 14, 21 and 29, embedded in Epon, and semi-thin serial sections were prepared. At designated intervals, histologic sections were treated with the direct fluorescein-labelled TUNEL method and immunostained for pancreatic hormones (glucagon, insulin) and apoptotic peptides [Bak, Bax, Fas, Fas ligand (FasL)], as well as for the anti-apoptotic peptide Bcl-2. All tissue sections were investigated using confocal laser scanning microscopy under identical setting for semiquantitative estimation of staining intensity. The percentage of apoptotic cells was between 1.6 and 2.1% and most apoptotic cells were beta-cells. Corresponding cells often contained Bak and Bax. Fas and FasL were mostly detected in islet cells within the first week after preparing the cultured suspension. The insulin content was low (1.1 +/- 0.22 ng per islet) directly after isolation. It then increased progressively up to day 14, after which it began to decrease. Glucagon expression, on the other hand, remained high for the entire duration of the investigation. In conclusion, the islet beta-cells may recover after the isolation procedure, but after 4 weeks in culture, both the insulin content and Bcl-2 staining decrease. Moreover, apoptosis is mediated by different mechanisms after the isolation procedure and after culturing the islets for 1 month. The present data may be important for further studies on isolated, cultivated or transplanted islets.
Animals↗
Cell-specific localization of G protein alpha-subunits in the islets of Langerhans.
G protein alpha-subunits are involved in the transduction of receptor-mediated regulation of insulin and glucagon secretions. To get further insight into the status of G proteins in alpha- and beta-cells of the Langerhans islets, we have used immunohistochemistry to study the distribution of alpha-subunits in pancreas sections from the rat. Our results show that only insulin-immunoreactive beta-cells display immunoreactivity for selective antibodies directed against the different members of the Galphas and Galpha12-families (alphas, alphaolf, and alpha12, alpha13 respectively). Immunoreactivities for antibodies directed against members of the Galphaq- and Galphai-families showed a more diverse localization: alpha11 and alphao2 were only detected in glucagon-immunoreactive alpha-cells, whereas alphai1 was detected in all beta-cells but only in a few alpha-cells. Even though beta-cells showed immunoreactivities for alphao-non-isoform-selective antibodies, we could not identify the isoform(s) present using selective alphao1 and alphao2 antibodies. Other members of the Galphai- and Galphaq-families (alphai3, alphat2, alphaz and alphaq) were detected in both alpha- and beta-cells. In conclusion, our findings demonstrate a clear difference in the localization of G protein alpha-subunits between alpha- and beta-cells, suggesting the involvement of specific receptor transduction pathways for the neuronal/hormonal regulation of alpha- and beta-cell functions.
Animals↗
[Non-functioning tumor of the islets of Langerhans].
About 15% of tumors of Langerhans, islets do not cause any hormone induced syndrome although they sintetise and secrete one or more regulatory peptides. These tumors are most frequently localised in the head and tail of the pancreas. They are usually greater then 5 cm. In diameter and present with pain, jaundice, palpable mass and malaise, rarely with variceal bleeding due to compression of the splenic vein. About 50% of the tumors present with symptoms caused by metastases. We present a 51 year old women in whom during the investigation for paraumbilical pain, predominantly on the left side a tumor of the tail of the pancreas was discovered and subsequently surgically removed. Standard histology showed a neuroendocrine tumor. Immunohistochemistry showed generalised immunoreactivity with antibodies against chromographin A, neuron specific enolasa and glucagon in more then 95% of cells. Somatostatatin was coexpressed in more then 5% of cells, PP in rare scattered cells. No reactivity was found for the other hormone markers. Ten years after surgery the patient has no signs of tumor recurrency.
Female↗
[Demonstration by immunofluorescence of somatostatin cells in the islets of Langerhans in 3 species of monkeys].
Indirect immunofluorescence technique with anti-somatostatin serum has allowed us to detect somatostatin containing cells in the Langerhans' islets of three species of monkeys (Macacus irus, Papio hamadryas, Cercopithecus aethiops). These cells are in close relationship with another cells, but occupy a more central position in the islets. Thus, the distribution of somatostatin-containing cells in the monkey's endocrine pancreas has not a similar pattern as in rodent's pancreas; they have a comparable topography as in the human islets but these cells are always more elongated than in the human islets. Only slight morphological differences are observed in the three species of monkeys.
Animals↗
[Diagnostic importance of the glucagon tolerance test in studying the islets of Langerhans apparatus of thyrotoxicosis patients].
Comparative studies of the glucagon-, OTTG- and BTTG tolerance test were performed in 50 patients, aged 25 to 50 years, glucagon being injected after intravenous and peroral glucose loading at hyperglycemic peak height. It was detected that a single intravenous glucagon injection provokes hyperglycemia mostly in healthy subjects than in patients with thyrotoxicosis during the first 15 to 30 minutes. Stimulating effect on insulin secretion was the same. Glucagon injection does not enhance glucose-induced hyperglycemia after peroral glucose loading and intensifies insulin rise rather than separate glucagon or glucose use. Combined glucagon-glucose administration produced tension in the insular apparatus alpha-cell function, that allows one to recommend this diagnostic test for determining reserve functional possibilities of Langerhans' islets in thyrotoxicosis-suffering patients with normal glucose tolerance under clinical conditions.
Adult↗
Gelatin density gradient for isolation of islets of Langerhans.
Isolation of islets of Langerhans (islets) has been performed by means of collagenase digestion of the pancreatic tissue combined with density gradient separation of islets from unwanted exocrine tissues. An enormous number of islets are necessary for clinical islet transplantation. The density gradient used for isolation of a large number of islets should satisfy several requirements in addition to those for the conventional density gradients, such as high viscosity for creating fine interfaces with a large area, easy sterilization, and low cost. This study is concerned with the development of a new density gradient made of low-molecular-weight gelatin. We isolated islets from the hamster pancreatic tissue using the gelatin density gradients. The yield and purity of islet and its insulin release function were compared with those of islets isolated using Ficoll and Ficoll-Conray density gradients that have been conventionally used. The new gelatin density gradient can separate islets from the unwanted exocrine tissue as effectively as the Ficoll density gradient and more effectively than the Ficoll-Conray density gradients. The islets collected using the gelatin gradient retain ability of insulin release increase in response to glucose stimulation, similar to those isolated by the Ficoll-Conray gradient and more than those collected by the Ficoll gradient. In addition, the gelatin effectively inhibited enzyme activities, that is, collagenase and proteolytic enzymes released from the exocrine tissue, and thus it can inhibit overdigestion of islets during their density gradient isolation. The gelatin gradient satisfies most of the additional requirements for islet isolation from the pancreatic tissue of large animals mentioned above. Although several factors, such as molecular weight of gelatin, osmolality of the gradient, and centrifugal conditions, still remain to be optimized, our results suggest that the gelatin gradient has potentiality to isolate islets from the pancreatic tissue of a large animal.
Animals↗