PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Islets of Langerhans”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2006

Integrin signaling via RGD peptides and anti-beta1 antibodies confers resistance to apoptosis in islets of Langerhans.

Islet transplantation is associated with a high rate of early graft failure caused by early immune attack and poor functionality of islets. Apoptosis of islet cells appears soon after islet isolation and primarily involves the beta-cell. The purpose of this study was to determine the effect of ligation to extracellular matrix (ECM) proteins on survival of the islets of Langerhans following islet isolation. Islets that had been cultured for 24 h on collagen type I showed an islet survival of 59.7 +/- 8.7%, while islets that had been cultured on collagen type IV and laminin showed an islet survival of 88.6 +/- 10.3 and 94.3 +/- 5.6%, respectively. Islets that had been pretreated with anti-beta1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed a decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and an increase of phospho-Akt Ser 473 activity by a factor of 3.1 and 2.9, respectively, compared with untreated islets. When detached from their natural ECM surrounding in the pancreas, islet cells undergo apoptosis, unless islets are cultured on collagen IV or laminin or treated with anti-beta1 integrin antibodies or RGD peptides to mimic ECM ligation. These results indicate that inhibition of anoikis may offer opportunities to improve function and viability of islet cells.

Animals↗
PubMed1977

[The immunofluorescence-microscopical evidence of insulin and glucagon in transplantated isolated Langerhans' islets in diabetic rats and dogs (author's transl)].

With the histochemical immunofluorescence technique were demonstrated the insulin and glucagon in the transplantated isolated Langerhans' islets in the liver at diabetic rats and dogs. Further on were tested the diabetic metabolic level with aid of clinico-chemical methods during the period of investigation (blood glucose, serum insulin, glucose tolerance test). It was found that after transplantation, 1 year by the rats and more than 8 weeks by the dogs, is existing a normoglycemic level. In the transplanted islets were seen a good immunofluorescence of insulin in the B cells and the glucagon in the A cells in all investigated stages.

Animals↗
PubMed1985

Effect of median eminence lesions and hormonal replacement on the prolactin receptors in the adrenal gland and Langerhans islets from ovariectomized adult rats.

The effect of hyperprolactinemia induced by median eminence lesions (MEL) and ACTH and glucocorticoid replacement on prolactin (Prl) receptors was studied in the adrenal, isolated Langerhans islets and the liver. Adult rats were ovariectomized 15 days before MEL and they were divided in the following groups: 1) SHAM: injected with saline solution 3 times in alternate days; 2) MEL: saline solution; 3) MEL + ACTH: 50 micrograms: 10 IU/rat, s.c. (Synacthen) and 4) MEL + DEXA: 10 micrograms/rat (dexamethasone). For measuring total lactogenic binding sites an in vitro treatment of the membrane fraction with 4M MgCl2 was used. MEL originated a significant increase in Prl serum levels, which was not altered by injections of ACTH or dexamethasone. In contrast, serum corticosterone (B) levels in MEL rats were significantly lowered, and it was restored by ACTH. Unexpectedly, B levels increased when dexamethasone was administered to MEL rats. Prl receptors were diminished in the adrenal gland and Langerhans islets from MEL animals, as compared with the SHAM group. ACTH and glucocorticoid administration did not affect the pancreatic Prl receptors, while the adrenal gland exhibited a further lowering of Prl binding sites during ACTH treatment. Since no effect was found when dexamethasone was injected, a possible direct action of ACTH is suggested. On the other hand, Prl receptors were induced in the liver by MEL, and this action was abolished by dexamethasone and ACTH. Binding affinity in every tissue studied remained unchanged. Our data suggest that endogenous Prl is able to regulate its own receptors not only in the liver, but also in the adrenal gland and pancreatic islets.

Adrenal Glands↗
PubMed1997

The role of Langerhans islets in pancreatic ductal adenocarcinoma.

An intimate relationship between the exocrine and endocrine pancreas has been convincingly demonstrated in recent years. Animal experiments have shed some light into the complex dialog between the two tissues. This interaction is pronounced in diseases of the pancreas, especially in experimentally-induced and human pancreatic cancers. New evidence highlights the importance of intact islets in the development of exocrine pancreatic cancer. Although tumors arise from large and small ducts, invasive and malignant adenocarcinomas of ductal phenotype also derive from stem cells within islets. Development of cancer within islets explains the association between pancreatic cancer and impaired glucose tolerance or diabetes. Hence, the previous epidemiological studies suggesting that diabetes is a predisposing factor for pancreatic cancer are refuted. The available evidence suggests that pancreatic cancer in a large number of pancreatic cancer patients ultimately leads to diabetes, and that removal of the tumors improves or cures the diabetes. Both in the hamster pancreatic cancer model and in patients, the development of cancer is associated with elevated plasma levels of islet amyloid polypeptide, which may be used as a tumor marker.

Adenocarcinoma↗
PubMed1997

Langerhans islet preparation in cell transplantation.

Islet cell transplantation is potentially one of the best techniques for the almost perfect symptomatic treatment of Type 1 diabetes mellitus. Thanks to the considerable progress achieved in isolating and purifying human islet cells, highly encouraging results have recently been reported. However, due to the need for immunosuppression treatment, the indications are presently as limited as those for transplantation of the vascularized pancreas, namely cotransplantation. The ultimate goal of transplantation is to allow long-term function of the grafted tissues using no or transitory host immunosuppression. When compared to solid organ grafts, cellular transplants are more amenable to creative strategies to accomplish this goal. We review the current status of islet transplantation in man and then the major steps before islet transplantation and their prospects.

Animals↗
PubMed2003

Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alphaTC6 cells, mouse clonal alpha-cells, and alpha-cells of islets of Langerhans.

Islets of Langerhans contain gamma-aminobutyrate (GABA) and may use it as an intercellular transmitter. In beta-cells, GABA is stored in synaptic-like microvesicles and secreted through Ca(2+)-dependent exocytosis. Vesicular inhibitory amino acid transporter (VIAAT), which is responsible for the storage of GABA and glycine in neuronal synaptic vesicles, is believed to be responsible for the storage and secretion of GABA in beta-cells. However, a recent study by Chessler et al. indicated that VIAAT is expressed in the mantle region of islets. In the present study, we investigated the precise localization of VIAAT in rat islets of Langerhans and clonal islet cells and found that it is present in alpha-cells, a minor population of F-cells and alphaTC6 cells, and clonal alpha-cells but not in beta-cells, delta-cells, or MIN6 m9-cells (clonal beta-cells). Combined biochemical, immunohistochemical, and electronmicroscopical evidence indicated that VIAAT is specifically localized with glucagon-containing secretory granules in alpha-cells. ATP-dependent uptake of radiolabeled GABA, which is energetically coupled with a vacuolar proton pump, was detected in digitonin-permeabilized alphaTC6 cells as well as in MIN6 m9 cells. These results demonstrate that functional neuronal VIAAT is present in glucagon-containing secretory granules in alpha-cells and suggest that the ATP-dependent GABA transporter in beta-cells is at least immunologically distinct from VIAAT. Because glucagon-containing secretory granules also contain vesicular glutamate transporter and store L-glutamate, as demonstrated by Hayashi et al., the present results suggest more complex features of the GABAergic phenotype of islets than previously supposed.

Adenosine Triphosphate↗
PubMed1986

The microvasculature of the human pancreas and its relation to Langerhans islets and lobules.

The 3-D relation between the lobules, terminal blood vessels and Langerhans islets of human pancreas was established by graphic reconstruction from serial histologic sections. The material included three pancreases obtained at autopsy. It was found that the lobule is an assembly of sublobular parenchymal units which have a terminal arteriole at the center. These, being considered to be an elemental structure of microcirculation, were named the "primary lobule" of the pancreas. The concept was also supported by the 3-D analysis of a pancreas "pseudolobulated" due to chronic venous congestion, in which "primary lobules" were clearly demarcated by atrophic zones distributed along the periphery of circulation. Four types of terminal arterioles were discriminated: 1) those terminating at an islet, 2) those having no relation with islet, 3) those with islets dispersed near the ending and 4) those coming directly from an interlobular artery. More than half the endings were found to belong to either Type 2 or 3, which was quite different from the traditional assumption of complete arterio-insular correlation. Consequently, islets could also be classified according to whether or not having an afferent arteriole, namely, into "arterial" and "non-arterial" islets. The "arterial" islets amounted to 75% in the total islet volume, although in islet number, the "non-arterial" ones accounted for as much as 72.5%. Thus, at least in man, functional correlation between islets and exocrine gland is not so tight as claimed by the insulo-acinar axis theory.

Adult↗
PubMedDate not supplied

[Isogenic islet transplantation on the rat liver (method for isolation and purification of the Langerhans islets)].

The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control. We have studied isogenic islet transplantation on the rat (WAG-RT1u) liver. The method of isolation and purification of the islets obtained 2.834 +/- 551.64 islets with purity of 83 +/- 2.45%. Diabetes was induced by streptozotocin and seric glucose prior transplantation was 35 mmol/L. The islet transplantation of 2.834 +/- 551.64 islets in the rat liver has normalized glucose test from 9.62 +/- 2.65 mmol/L 10 days after transplantation to 7.43 +/- 0.27 mmol/L later in the follow-up (P < 0.05). The median survival time of the islets was 73 days. In conclusion both the method of isolation and purification of the islets and islet transplantation was effective in the control of the diabetes induced by streptozotocin with median survival time of both islet and rat more than 73 days when rats were sacrified.

Animals↗
PubMedDate not supplied

Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans.

Islet transplantation therapy would be applicable to a wider range of diabetic patients if donor islet acceptance and protection were possible without systemic immunosuppression of the recipient. To this aim, gene transfer to isolated donor islets ex vivo is one method that has shown promise. This study examines the combined effect of selected immunomodulatory and anti-inflammatory genes known to extend the functional viability of pancreatic islet grafts in an autoimmune system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The length of time the recipient remained euglycemic was used to measure the ability of the transgenes to protect the graft from autoimmune destruction. Although the results of these cotransfections gave little evidence of a synergistic relationship, they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic T cells.

Adenoviridae↗
PubMed1996

[Isolation and cryopreservation of human islets of Langerhans].

Islet transplantation represents an alternative to whole pancreas transplantation for the treatment of patients suffering from diabetes type I. The transplantation of a sufficient number of islets is an essential condition for successful allograft. Islet cryopreservation allows the storage of islet preparations for subsequent pooling, at the time of transplantation, of cryopreserved islets with a fresh preparation in order to increase the mass of transplanted pancreatic endocrine tissue. From May 1994 to April 1995, islets were isolated from 22 human pancreases using a modified automated method, and 19 preparations were cryopreserved. The function of cryopreserved islets was tested in vitro (static incubation and perifusion). The results of static incubation experiments confirmed that the insulin secretion of cryopreserved human islets in response to glucose stimulation was comparable to the response of islets that have not been frozen. In static incubation experiments, the mean (+/- SEM) insulin secretion of islets, prior to cryopreservation, was 239.3 (+/- 58.9) and 479.5 (+/- 59.5) pg/islet/15 min at 2.8 mM glucose and 16.7 mM glucose respectively. The mean (+/- SEM) insulin secretion of cryopreserved islets was 274 (+/- 103.2) and 468.5 (+/- 191.9) pg/islet/15 min at 2.8 mM and 16.7 mM glucose respectively. The perifusion experiments also demonstrated a significant increase of insulin secretion from cryopreserved islets perifused with a stimulating glucose concentration. Our experiments allow us to envisage the use of cryopreserved islet preparations for allotransplantation in diabetic patients.

Adult↗
PubMed1977

[Computer analyse of ultrahistochemical observed metal containing secretory granules in Langerhans islets cells of normoglycemic and diabetic rat].

Metal-containing secretory granules of alpha 2-cells of the LANGERHANS' islets of normal and alloxan-diabetic rats were stained for electron microscopy by a special method. Thereafter the electron micrographs were analysed by the Quantimet 720 image analysing computer with respect to size of the granules and their quantitative distribution in classes. The following statistical tests verified significant differences between the distributions of the secretory granules under normal and diabetic conditions. The secretory granules from alloxan-diabetic animals were diminished distinctly. The examination by image analysing computer confirmed objectively observations, we have made and published formerly.

Animals↗
PubMed1982

Effect of corticosterone upon insulin biosynthesis and storage by isolated rat Langerhans islets.

A rapid inhibitory effect of corticosterone upon glucose- or leucine-induced insulin release being established, steroid action upon insulin biosynthesis of rat Langerhans islets was studied as a function of time. Islet proinsulin and insulin content was reduced after two hours of incubation in presence of corticosterone (0.2 mg/l) with a 16.7 mmoles/l glucose stimulation. L (-) [4-5(3)H] leucine incorporation into proinsulin and insulin was lowered at all time (points examined: 1, 2 and 3 hours). Incorporation ratio between proinsulin and insulin remained stable, so an interaction at the proinsulin biosynthetic level may be possible. Corticosterone had no effect upon biosynthesis of other islet proteins. Our data suggest that the corticosterone inhibition of insulin biosynthesis is specific.

Animals↗
PubMed1979

[Autotransplantation of Langerhans' islets in a case of total duodenopancreatectomy (author's transl)].

A 36-year-old man suffering from chronic pancreatitis involving the whole organ had total duodenopancreatectomy. The Langerhans' islets were isolated from the extirpated organ and transplanted into the liver via portal artery. Insulin substitution could be lowered from 50 I.U. to 12 I.U. by the 5th post operative day. Repeatedly, raised insulin levels could be verified in response to high blood sugar loads. C-peptide and glucagon were also found. 7 months after transplantation the islets still seem to be functioning.

Adult↗
PubMed1987

Dissociation of Langerhans islets in the rabbit after pancreatic duct ligation. Immunocytochemical and ultrastructural studies.

In the rabbit, pancreatic duct ligation leads to serious disturbances of the pancreatic endocrine parenchyma. Immunocytochemical studies conducted over a short period (between 5 and 30 days post ligation) allow observation of a progressive dissociation of the Langerhans islets which initially affects the splenic part of the pancreas, a region where numerous large islets are found. This dissociation is followed by a dispersion of small heterologous endocrine cell clusters or isolated endocrine cells in a connective tissue which replace the exocrine parenchyma. On the 30th day after ligation ultrastructural studies show marked degranulation of the B cells demonstrating the great fragility of these cells. These observations of insular dissociation, scattering of the different endocrine cells and impairment of B cells are often reported in experimental and pathological studies of the pancreas.

Animals↗
PubMedDate not supplied

Effects of somatostatin deficiency on cell distribution within the Langerhans islets.

Insulin, glucagon and somatostatin (SLI) in the pancreas and the gastrointestinal tissue of rats were measured following a high (300 mg/kg) or low (150 mg/kg) dose of cysteamine, given intermittently for 14 days. In addition, the effect of prolonged cysteamine-induced depletion of pancreatic SLI upon the cell distribution within the Langerhans islets was compared with that of chronic insulin-deficient rats produced by streptozotocin. The high or low dose of cysteamine reduced pancreatic SLI to 8.3% and gastrointestinal SLI to 5.6% of control levels without duodenal ulcer. The high dose of cysteamine also reduced pancreatic insulin to 37% of controls without hyperglycemia. No change in the glucagon concentration was observed. In SLI-deficient rats, distribution of A and B cells was similar to that of controls, even though D cells were rarely seen. In insulin-deficient rats, however, the number of A and D cells per islet area increased with a concomitant decrease in B cells. Intermittent administration of a low dose of cysteamine, thus, appears to be useful to produce a chronic SLI-deficient rat. However, a high dose of cysteamine is not a specific depletor of pancreatic SLI. Although insulin may be important to maintain normal cell distribution within the islets, pancreatic SLI may not have such a role.

Animals↗