Islet graft-induced changes of beta-hydroxybutyrate dehydrogenase and glucose-6-phosphatase activity in liver cells of diabetic recipient rats.

It is known that the liver is a favourable site for implantation of pancreatic islets since the grafted islets remain metabolically intact and provide long-term normoglycemia in diabetic animals. However, the long-term effects exerted by the grafted tissue on the host organ are not well defined. We therefore investigated by light and electron microscopy the effects of syngeneic islets on the host organ after intraportal transplantation into the liver of streptozotocin (STZ)-induced diabetic LEW.

Glucose transporter isoform (GLUT) 2 expression in beta-cells of long-term syngeneic islet grafts.

Syngeneic islets were transplanted into the liver of streptozotocin (STZ)-induced diabetic LEW.1W rats, and the expression of the glucose transporter isoform GLUT 2, an essential component of the glucose-sensing mechanism of the pancreatic beta-cell, was determined in the grafted islet tissue. Graft-bearing liver was obtained 12, 36, and 60 weeks after transplantation, and tissue sections were immunoperoxidase stained for GLUT 2 and major islet peptides.

Reinnervation of pancreatic islets and regulation of insulin secretion by hepatic sympathetic nerves after intraportal transplantation of islets into livers of diabetic rats.

It was the aim of this study to elucidate whether intraportally transplanted pancreatic islets were reinnervated after transplantation and whether the secretion of insulin from pancreatic islets might be modulated by the vegetative innervation of recipient livers. Two weeks after intraportal transplantation of 2000 neonatal pancreatic islets recipient rats completely recovered from streptozotocin-induced diabetes. Predominantly catecholaminergic, but also cholinergic nerve fibers were detected in islet cell complexes between beta-cells.

Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves.

Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood, and by a disappearance of polyuria and polydipsia. The reversal remained stable for at least 9 months.

[Tritium-thymidine autoradiography of the rat pancreas after alloxan-induced diabetes mellitus].

Knowledge of pancreatic cells and their proliferation has proved to be essential to better understanding of the pathogenesis, clinical course, and prognosis of pancreatic diseases. Studies had been conducted by means of in vivo autoradiography into pancreatic cell proliferation in normal rats of various age groups (Laucke and Müller 1988; Müller et al. 1990).

[Proliferation of beta cells after syngeneic transplantation of isolated Langerhans cells into the spleens of diabetic rats].

Syngeneic transplantation of cultured and functionally characterized neonatal islet into the spleen of streptozotocin diabetic Lewis rats resulted in long time survival up to 200 days and in plasma glucose levels lower than 9 mmol/l. The daily plasma glucose profile of transplanted rats had shown significantly above that of non diabetic control rats. 200 days after transplantation morphologically intact, insulin containing beta-cells were demonstrable in the spleen, thus demonstrating the long-term survival of functioning islet cells.

Pancreatic cell proliferation in normal rats studied by in vivo autoradiography with 3H-thymidine.

In vivo 3H-Thymidine autoradiographic investigations of DNA synthesis in acinar, islet and duct cells in the pancreas of normal rats showed that activity was dependent on age. The proliferation of acinar and islet cells, which was high in young animals, decreased exponentially with age; proliferation of the ductal cells on the other hand, increased until the animals became mature. These findings suggest that the physiological regeneration of acinar and islet cells, as well as their replacement after injury in adult animals commences from pancreatic ducts.

Morphological findings in the liver of diabetic rats after intraportal transplantation of neonatal isologous pancreatic islets.

Morphological (light microscopical, immunohistological and electron microscopical) findings in the recipient liver of rats with streptozotocin-induced diabetes, obtained 9 months after intraportal injection of neonatal isologous pancreatic islets, are described and their significance discussed. The results support the assumption of active ingrowth of nonmyelinated nerve fibers into the islet isografts. The hepatocytes surrounding the islet isografts contain--obviously owing to the influence of unusually high and locally variable concentrations of insulin--a focally increased number of enlarged mitochondria, abundant glycogen and a smaller amount of neutral fat droplets.

Ducto-insular proliferation of beta-cells after syngeneic islet transplantation into the spleen of streptozotocin-diabetic Lewis rats.

Syngeneic transplantation of cultured and functionally characterized neonatal islets into the spleen of streptozotocin diabetic Lewis rats resulted in long time survival up to 200 d and in plasma glucose levels lower than 9 mmol/L. The daily plasma glucose profile of transplanted rats had shown significantly above that of nondiabetic control rats. Two-hundred d after transplantation, morphologically intact, insulin containing beta-cells were demonstrable in the spleen, thus demonstrating the long-term survival of functioning islet cells.

Syngeneic transplantation of rat pancreatic islets into the spleen. Light and electron microscopical findings.

An islet transplantation model was established with the two congeneic Lewis rat strains LEW.1W and LEW.1A, which were made diabetic by a single i.

Electron microscopical investigations on lymphocyte cytotoxicity against beta-cells in recent onset IDDM.

The effect of lymphocytes from patients with newly diagnosed insulin dependent diabetes on isolated rat or human islets during a 20 h in vitro incubation was investigated by morphological and biochemical methods. All stages of target cell reaction of lymphocytes against beta-cells were observed. Cytoplasmic projections towards and contacts with beta-cells, circumscribed lysis of the outer cell membrane at the contact side and complete lysis of beta-cells were seen.

Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique.

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases.

[Intermediate cells in the pancreas and cell transformation].

The paper reviews the medical literature concerning the occurrence and several possible explanations of the origin nature of pancreatic intermediate cells present. Electron microscopic studies of the human pancreas and results of animal experiments in the last years strongly suggest that cells in the wall of small pancreatic ducts (ductules) may develop into duct cells, exocrine pancreatic cells (acinar cells), endocrine islet cells, and hepatocytes even in the adult organism. This suggests that transitional cells arise from the known types of pancreatic intermediate cells during this process.

Electron microscopic demonstration of intermediate cells in the healthy adult human pancreas.

Electron microscopic findings obtained from the pancreas of a healthy 26-year-old organ donor are reported. These findings suggest for the first time that intermediate cells (i.e.

Low dose streptozotocin induced diabetes in mice. Metabolic, light microscopical, histochemical, immunofluorescence microscopical, electron microscopical and morphometrical findings.

The experimental animal model of human insulin-dependent diabetes mellitus (IDDM, type I diabetes), which was for the first time described by Like and Rossini (1976) for Charles River CD-1 mice and produced by the application of multiple subdiabetogenic streptozotocin (SZ) doses, has been reproduced in the mouse strain C57 Bl/KsJ which has been bred over several generations at the Central Institute for Diabetes Karlsburg (since 1975). Male mice were given subdiabetogenic intraperitoneal injections of SZ (40 mg/kg b.w.

[Electron microscopic findings in A-cells of the islands of Langerhans in diabetes mellitus].

A description is given of the electron microscopic-morphometric findings obtained for the islets of Langerhans of the pancreas and for the glucagon-producing A cells of one patient suffering from longstanding insulin-dependent diabetes mellitus (IDDM, type I diabetes), two patients with longstanding insulin-independent diabetes mellitus (NIDDM, type II diabetes), and one non-diabetic. A morphometric determination of the volume densities of the vascular connective tissue and the various endocrine cells per islet tissue and organelles/ultrastructures per A cell was made, and the diameters of the A-granules were measured. So far, no such studies have been made for human diabetes mellitus, and only a few are available for humans with sound metabolism.

Simultaneous biochemical and morphological investigations on the effect of leukocytes from type I diabetics on isolated rat islets.

The first morphological and biochemical findings on the effect of leukocytes from a newly diagnosed type I diabetic patient on isolated rat islets are presented. Leukocytes from venous blood were co-incubated with isolated neonatal rat islets for 22 h. According to the biochemical and electron-microscopical findings, beta cells localized in the periphery of the islets and a few single beta cells show lytic alterations (single cell necroses).

Morphologic-histochemical characterization of inflammatory cells in insulitis induced by multiple subdiabetogenic doses of streptozotocin in C57B1/KsJ mice.

Insulitis can be induced in C57B1/KsJ mice by injection of subdiabetogenic doses of streptozotocin (SZ, 40 mg/kg body weight) on five consecutive days. Subsequent to the resulting insulitis, a persisting diabetes syndrome develops. This experimental diabetes is regarded as a model of insulin-dependent diabetes mellitus in man (IDDM, type I).

Intermediate cells in the adult human pancreas. Contribution to the transformation of differentiated cells in vertebrates.

Problems associated with the transformation of differentiated cells in vertebrate organisms are discussed based on electron microscopical results of intermediate cells (i.e. cells with morphological characteristics of exocrine acinar cells and endocrine cells of Langerhans' islets) in the pancreas of human adults with chronic insulin-dependent diabetes mellitus.

Ultrastructural, immunohistological, and clinical findings in the pancreas in insulin-dependent diabetes mellitus (IDDM) of long duration.

Electron microscopical and immunohistological findings in small biopsies obtained at surgery from two subjects with longstanding type-I-diabetes [insulin-dependent diabetes mellitus (IDDM)] are described and demonstrated in relation to clinical data. The main findings are the first electron microscopical demonstration of A cells scattered as single cells in the exocrine pancreatic tissue and the detection of intermediate cells of the acinar-A cell type. Intermediate cells have never been reported before in the pancreas of diabetes in man.

[A careful method for the collection of pancreatic tissue for special morphological and biochemical studies].

The examination of pancreas tissue is of essential necessity for special diagnostic problems and for the clarification of the etiology of pancreas diseases. The needle biopsy--mostly used--not always delivers sufficient material and is combined with uncontrollable complications. A new method is described in this paper which allows to obtain specimens of the pancreas during abdominal operations in a safty manner.