Pancreatic islet cell tumors metastatic to the liver: treatment by hepatic artery chemo-embolization

The embolization of hepatic metastases of pancreatic islet cell tumors achieves a tumor necrosis without liver failure owing to double hepatic blood supply. The arterial chemotherapy performed at the same time delivers a large amount of cytotoxic agent directly into the tumor. Tumor bulk reducing and decreasing of production of pharmacologically active substances may be obtained to some degree. Although an objective documentation of the therapeutic effect is difficult to obtain, several series emphasize that the embolization provides a partial and transient palliative remission. Therefore, the chemo-embolization should be included in a multidisciplinary approach of metastatic endocrine malignancies in combination with surgical resection, systemic antineoplastic chemotherapy, and antihormonal therapy.     

Pancreatic islet response to hyperglycemia is dependent on peroxisome proliferator-activated receptor alpha (PPARalpha)

This study tests the hypothesis that islet peroxisome proliferator-activated receptor alpha (PPARalpha) influences insulin secretion. Freshly isolated islets of normoglycemic PPARalpha-null mice display no major alteration of glucose-stimulated insulin release. However, after 24 h of culture in high glucose, PPARalpha-null islets exhibit elevated basal insulin secretion and fail to increase insulin mRNA. 24-h culture with palmitate replicates this phenotype in wild-type islets. The data suggest that PPARalpha is needed to ensure appropriate insulin secretory response in situation of short-term hyperglycemia, likely by maintaining islet lipid homeostasis. As such, islet PPARalpha could contribute to delay the progression of type 2 diabetes.     

Islet alpha cell number is maintained in microencapsulated islet transplantation

Islet transplantation can reverse hyperglycaemia in Type 1 diabetes patients. One problem in islet transplantation is a loss of beta cell mass as well as blunted glucagon responses from the grafted islets. It has been suggested that alpha cell loss is associated with close contact of the alpha cells with the implantation organ. In the present study we made use of microencapsulation, where transplanted islets are not in direct contact with the host implantation site. After transplantation, the number of glucagon cells stained per microencapsulated islet section was increased whereas the number of insulin cells stained was decreased. DNA content of the islets was reduced, as was insulin content, whereas glucagon content was unchanged. This indicates that cell number in transplanted microencapsulated islets diminishes, which can be accounted for by loss of beta cells. However, in contrast to previous studies using non-encapsulated islets, alpha cell number seems to be maintained.     

Pancreatic polypeptide and glucagon: Non-random distribution in pancreatic islets

When the technique of immunofluorescence is applied to rat pancreas to detect insulin, glucagon, somatostatin and pancreatic polypeptide (PP), two populations of islets having distinct cellular content and topographical distribution can be recognized. Islets from the lower part of the head show a well-defined rim of PP-containing cells, but very few or no glucagon-containing cells. Islets from the body and tail display the familiar rim of glucagon-containing cells and possess very few or no PP-containing cells. This inverse relationship between glucagon and PP-cells in different parts of the pancreas means that caution must be exercised when interpreting functional or morphological observations using different pancreatic fractions.     

Pancreatic polypeptide (PP)- and glucagon cells in the pancreatic islet of Xiphophorus helleri h. (Teleostei)

Summary Correlative immunohistochemical and electron microscopical studies on the pancreatic islet of the teleost fish Xiphophorus helleri using antibodies to pancreatic polypeptide (PP) and glucagon show that separate cell types are responsible for the production of these peptides. The PP-cells correspond to the previously described A2-cells with round granules, while the A2-cells with crystalline granules are the true glucagon cells. An earlier suggestion that there are two types of glucagon cells in teleost islets is therefore withdrawn.A portion of the results has been presented at Colloque annuel de la Société Française de Microscopie électronique, Lyon-Villeurbanne, 21–23 Mai 1979. Study supported in part by the Medical Research Council     

Pancreatic islet beta-cell and oxidative stress: the importance of glutathione peroxidase

Pancreatic beta-cell function continuously deteriorates in type 2 diabetes despite optimal treatment regimens, which has been attributed to hyperglycemia itself via formation of excess levels of reactive oxygen species (ROS). Glutathione peroxidase GPx), by virtue of its ability to catabolize both H(2)O(2) and lipid peroxides, is uniquely positioned to protect tissues from ROS. The level of this antioxidant in beta cells is extremely low and overexpression of GPx in islets provides enhanced protection against oxidative stress. This suggests that GPx mimetics may represent a valuable ancillary treatment that could add a novel layer of protection for the beta-cell.     

The genetics of hyperekplexia: more than startle!

Hyperekplexia is characterised by neonatal hypertonia and an exaggerated startle reflex in response to acoustic or tactile stimuli. Genetic analysis of this disorder has revealed mutations in genes for several postsynaptic proteins involved in glycinergic neurotransmission, including the glycine receptor (GlyR) alpha1 and beta subunits, gephyrin and collybistin. However, new research suggests that mutations in the gene encoding the presynaptic glycine transporter GlyT2 are a second major cause of human hyperekplexia, as well as congenital muscular dystonia type 2 (CMD2) in cattle. These findings raise the intriguing possibility that both presynaptic and postsynaptic causes of disease might also exist in related disorders, such as idiopathic generalised epilepsies, where mutations in inhibitory GABA(A) receptor subunit genes have already been identified.     

Pancreatic and gut hormones during fasting: insulin, glucagon, and somatostatin

When adult male rats were fasted for 24 or 72 h there was no change in the pancreatic content of insulin or glucagon, but the somatostatin content increased at 72 h. This contrasts with earlier reports of reduced pancreatic somatostatin after fasting. After a 48-hour fast there was an increase in the concentration of duodenal somatostatin, and a tendency toward reduced concentrations in stomach, jejunum, and ileum. When duodenal mucosa and muscle extracts were chromatographed the relative amounts of putative somatostatin-28 and somatostatin-14 were unchanged. Insulin secretion from the perfused pancreata of 72-hour-fasted rats was markedly reduced, but glucagon and somatostatin secretion was indistinguishable from that of fed controls. These results indicate that in spite of the marked alterations of nutrient metabolism and insulin secretion which occur during fasting, the pancreatic content of insulin, glucagon and somatostatin and the gut concentration of somatostatin are well maintained.     

A mark in the core: silence no more!

The histone modification repertoire has recently been expanded. Dot1p is a new type of methyltransferase that methylates lysine 79 in the histone H3 core only in its nucleosomal context and has a possible role in marking open chromatin regions.     

The pancreatic islet endothelial cell: emerging roles in islet function and disease

The pancreatic islets are one of the most vascularized organs of the body. This likely reflects the requirements of the organ for a rich supply of nutrients and oxygen to the tissue, as well as the need for rapid disposal of metabolites and secreted hormones. The islet endothelium is richly fenestrated to facilitate trans-endothelial transport of secreted hormones, has a unique expression of surface markers, and produces a number of vasoactive substances and growth factors. The islet endothelial cells play a critical role in the early phase of type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing receptors, thereby enabling immune cells to enter the endocrine tissue and cause beta-cell destruction. Following transplantation, pancreatic islets lack a functional capillary system and need to be properly revascularized. Insufficient revascularization may severely affect the transport properties of the islet endothelial system, resulting in a dysfunctional islet graft.     

The pancreatic islet endothelial cell: emerging roles in islet function and disease

The pancreatic islets are one of the most vascularized organs of the body. This likely reflects the requirements of the organ for a rich supply of nutrients and oxygen to the tissue, as well as the need for rapid disposal of metabolites and secreted hormones. The islet endothelium is richly fenestrated to facilitate trans-endothelial transport of secreted hormones, has a unique expression of surface markers, and produces a number of vasoactive substances and growth factors. The islet endothelial cells play a critical role in the early phase of type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing receptors, thereby enabling immune cells to enter the endocrine tissue and cause beta-cell destruction. Following transplantation, pancreatic islets lack a functional capillary system and need to be properly revascularized. Insufficient revascularization may severely affect the transport properties of the islet endothelial system, resulting in a dysfunctional islet graft.     

Pancreatic hormones disappearance after total pancreatectomy in the duck: correlation between plasma glucagon and glucose

The decline of 3 plasma pancreatic hormones, glucagon (G), insulin (I) and somatostatin (S) was studied in fasting ducks after total pancreatectomy. The results show that the decrease of plasma glucose is highly correlated with the disappearance of G, while no important variation of the G/I ratio occurs during the period of observations (80 minutes) the animal being kept fasted. No participation of pancreatic S in glucose metabolism could be detected, the origin of peripheral S in the fasting state seeming due to the intestine for about 50%.     

Immunohistochemical localization of glucagon and pancreatic polypeptide on rat endocrine pancreas: coexistence in rat islet cells

We used immunofluorescence double staining method to investigate the cellular localization of glucagon and pancreatic polypeptide (PP) in rat pancreatic islets. The results showed that both A-cells (glucagon-secreting cells) and PP-cells (PP-secreting cells) were located in the periphery of the islets. However, A-cells and PP-cells had a different regional distribution. Most of A-cells were located in the splenic lobe but a few of them were in the duodenal lobe of the pancreas. In contrast, the majority of PP-cells were found in the duodenal lobe and a few of them were in the splenic lobe of the pancreas. Furthermore, we found that 67.74% A-cells had PP immunoreactivity, 70.92% PP-cells contained glucagon immunoreactivity with immunofluorescence double staining. Our data support the concept of a common precursor stem cell for pancreatic hormone-producing cells.Key words: glucagon, pancreatic polypeptide, rat, pancreas, Immunofluorescence double staining histochemistry.The pancreatic islet is comprised of numerous cell types that synthesize and secrete distinct peptide hormones. Four major cell types are recognized in pancreatic islets of many mammalian species including rat, A-cells which contain glucagon, B-cells which contain insulin, D-cells which contain somatostatin, and PP-cells which contain the pancreatic polypeptide (PP) (Erlandsen, 1980; Reddy et al., 1988).Previous studies have revealed coexistence of glucagon- and PP-like immunoreactivity in endocrine pancreas cells of frog, rat, baboon, murine, monkey, and fish (Kaung and Elde, 1980; Kaung, 1985a, 1985b; Wolfe-Coote et al., 1988; Herrera et al., 1991; Lozano et al., 1991; Park and Bendayan, 1992; Louw et al., 1997). However, those experiments were performed by staining adjacent ultrathin sections with anti-glucagon serum and anti-PP serum respectively by peroxidase antiperoxidase (PAP) or immuno-gold labeling or avidin-biotin-peroxidase method, and the situation of two kinds of positive cells were compared.It is still not clear whether one cell type contains two or more peptides. Therefore, we used immunofluorescence double staining to identify the peptides secreted by single specific cells.This is the first time that coexistence of glucagon and PP in rat islet cells has been detected by an immunofluorescence double staining method.     

Immuno-overlay: A method for identification of hepatoma cell colonies that secrete albumin

Summary A screening technique was developed for the identification of clones of hepatoma cells that secrete albumin. The technique employs the overlay of a 1% agarose solution containing antiserum to albumin onto clones of hepatoma cells. A distinct immunoprecipitation complex is formed in the immuno-overlay that corresponds directly to the position of each secreting clone. Clones deficient in albumin secretion do not form an immunoprecipitate. Thus comparison of the immuno-overlay and the cell colonies results in identification of variant clones as well as those capable of secretion. Biochemical characterization of the region of agarose overlay from secreting and nonsecreting clones demonstrates the specificity of the method and its potential for selection of colonies that are secreting other hepatic or cellular proteins. This study was supported by Grant GM 22372 from the Public Health Service. G. J. D. is a recipient of an Established Investigatorship from the American Heart Association.