摘要:

The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-g), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p <0.05 and <0.01, respectively) and also significantly enhanced CCK-stimulated amylase secretion (p <0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p <0.001). However, concentration levels of 1–100 pmol/ml galanin did not affect CCK-%stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Galanin-like immunoreactivity (GalLI) was found to be present in extracts taken from human, canine, and porcine pancreata. The dominant gel filtration peak in each species co-elutes with standard synthetic porcine galanin (Gal), but an apparently smaller molecular weight Gal form was present in human pancreas and intestine and in dog intestine. Reverse-phase HPLC demonstrated identity of porcine pancreatic Gal immunoreactivity with synthetic intestinal Gal. Heterogeneity was seen on reverse-phase HPLC: Human pancreas and intestine had three peaks of immunoreactivity; the retention times were identical between the pancreas and intestinal extracts; and human Gal elutes at an earlier retention time than porcine Gal. Similarly, dog pancreatic GalLI eluted earlier than porcine Gal on reverse-phase HPLC. Immunohistochemical studies revealed the presence of specific staining for GalLI in varicose nerve fibers in the pancreas of the three species. In the dog pancreas an association between Gal-containing nerve fibers and islet cells was readily demonstrable. This was not the case with pig or human pancreas. We conclude that pancreatic Gal is present in the pancreas of the three species and that molecular heterogeneity is similar between intestinal and pancreatic forms. In the dog, a distinct anatomical relationship is demonstrable between Gal-containing nerves and islet cells.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Galanin and norepinephrine (NE) both occur in adrenergic nerves in the pancreas. Since they are co-released from the nerve terminals and both inhibit glucose-induced insulin release, we investigated in the mouse if they cooperate in exerting this effect. When administered alone in vivo, both galanin (50–530 pmol/kg) and NE (40–320 nmol/kg) dose-dependently inhibited the increase in plasma insulin levels at 1 min following intravenous injection of glucose (2.8 mmol/kg). When galanin and NE were given together at different dose levels, no potentiating effect on the inhibition of the glucose-induced plasma insulin response was observed. In vitro, in overnight cultured mouse islets, both galanin (10−9−10−6M) and NE (10−9−10−6M) in a dose-related manner inhibited the insulin release induced by 11.1 mMglucose. Galanin (10−9M) did not further enhance the inhibited insulin response evoked by NE (10−9−10−6M.) Thus, no functional evidence exists, either in vivo or in vitro, that galanin and NE potentiate the inhibitory action of each other on glucose-induced insulin release in the mouse.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study was conducted to clarify the quantitative and qualitative changes in the cells of the islets of Langerhans in the autotransplanted pancreas in dogs and to correlate these changes with alterations of glucose tolerance. The left lobe of a canine pancreas was transplanted into the left iliac fossa. The splenic vessels were anastomosed to the left iliac vessels. The pancreatic duct was left open to the peritoneal cavity. Open biopsies of the autotransplanted pancreas were performed 3, 7, 11, and 14 weeks after transplantation. The islets in the transplanted pancreas were examined ultrastruc-turally; B-cells, A-cells, and D-cells were identified immunohistochemically and their percentages were determined. Intravenous glucose tolerance tests were performed 3, 5, 7, 11, and 14 weeks after operation, and several indexes (Kvalues and integrated response and increased values for baseline serum and immunoreactive insulin) were calculated. Fibrosis of the transplanted pancreas progressed after transplantation. The percentage of B-cells fell significantly (p <0.01), whereas that of A-and D-cells did not have significant changes. The ultrastructural study revealed an increase in collagen bundles, degranulation of B-cells, and marked preservation of A-cell granules 3 weeks after transplantation. B-Cells with dark cytoplasm were found 7 weeks after operation. In contrast, clusters of immature B-cells were seen in some sections of the pancreas 14 weeks after autotransplantation. The integrated response in baseline serum was increased significantly (p <0.01), and theKvalue was decreased significantly (p <0.01) 11 weeks after autotransplantation when compared with the initial posttransplant period. On the other hand, 14 weeks after autotransplantation, neither the integrated response in baseline serum nor theKvalue showed significant difference from the initial posttransplant period. It may be that the trend toward slight recovery of glucose metabolism 14 weeks after autotransplantation was associated with the clusters of immature B-cells observed ultrastructurally, although the number of B-cells was relatively decreased. Further studies must be done to clarify this phenomenon.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Near-total pancreatectomy in a neonate presenting with persistent hypoglycemia offered an unusual opportunity to grow preparations enriched in β-cells. Morphology, chromosomal analysis, and immunohistochemistry were used to characterize a subculture (Nesi B) that remained stable through passage 11. Insulin secretion of Nesi B was constitutive at 38–74 nU/μl of medium/ 24 h, increasing modestly in the presence of isobutylmethylxanthine, an inhibitor of cyclic AMP phosphodiesterase. Endocrine cells, exclusive of those in islet regions, were widely distributed throughout the original tissue section, and immunostaining of the Nesi B subculture demonstrated well-differentiated heavily granulated insulin-positive cells, each with a normal modal number of chromosomes (46). Nesi B cell-associated macromolecules were isolated in 3 × 10−3ethylenedinitrilotetraacetate/phosphate-buffered saline and were found to be reactive with a heterologous immune serum elicited to a cloned rat pancreatic β-cell line (RIN-SF). Western (immuno) blotting showed this immunoreactivity to reside primarily in a 95-kDa fraction of Nesi B-derived components. These results indicate that human nesidioblasts can be cultured for a sufficient number of passages to allow isolation and immunochemical characterization of pancreatic β-cell macromolecules shared between rat and human and that may serve as organ-specific antigens for inflammatory disorders of the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. Induction of ornithine decarboxylase (ODC) activity is one of the early events triggered in proliferating cells. Our aim was to study the effect of bFGF on ODC activity and ODC mRNA expression in a pancreatic tumoral cell line, AR4-2J. Following kinetic and dose-response studies, we found that maximal stimulation (150% over control) of ODC activity occurred after 3 h of bFGF treatment (10−9M), the EC, being 20 pM.To elucidate the mechanism by which bFGF stimulates ODC activity, we measured the ODC mRNA levels by Northern blot hybridization using a32P-labeled rat cDNA probe. In AR4-2J cells treated with bFGF at 10−9Mover 120 min, ODC mRNA expression was transiently increased by 71.6% at 60 min. Furthermore, bFGF was also able to stimulate ODC mRNA synthesis in the presence of cycloheximide. In conclusion, in AR4-2J cells of pancreatic origin, bFGF stimulates ODC gene transcription. This effect contributes to the stimulation of ODC enzymatic activity and to the proliferative effect of bFGF on this cell line.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Autotransplantation of the distal pancreas segment with pancreaticojejunostomy was performed in four patients with cancer of the head of the pancreas to preserve endocrine pancreatic function after extended total pancreatectomy. All patients had tumor involvement of both the celiac axis and the portal vein. The pancreatic graft was determined to be cancer-free by frozen section histologic and pancreatic juice cytologic examinations. The distal pancreas segment was autotransplanted to the iliac vessels heterotopically and placed in the extraperitoneal pocket to avoid untoward effects of any local recurrence or pancreatic leakage. This procedure, in the form of reconstruction, might be called modified subtotal pancreatoduodenectomy. Postoperatively, all patients remained normoglycemic without exogenous insulin administration, and their quality of life was considered satisfactory.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Stereological analysis of rat endocrine pancreas was carried out after 4 months of low-protein intake. Thirty male Wistar rats, aged 2 months at the beginning of the experiment, were divided into three groups. The control group (NP) received a standard laboratory diet. The experimental group (LP) received a low-protein diet, and the pair-fed animals also received a standard laboratory diet, as the NP rats did, but restricted to the amounts consumed by the LP group. All groups were offered drinking water ad lib. Weibel's multipurpose lattice was used to determine the volume fraction of cells and numerical density of islets in the endocrine pancreas. The results showed that the long-term low-protein diet decreased the volume fraction of B-cells and increased that of A-cells. Numerical density of islets was significantly increased, whereas the absolute number was decreased. The mean number of B-cells per islet was found to be decreased and that of D-cells increased. The mean radius of the islets was decreased, as was the mean surface area.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To clarify the relationship between the diminution of the serum protease inhibitor capacity and the severity of pancreatitis, the binding capacity of serum protease inhibitors for exogenous elastase 1 (El) was investigated by gel filtration, the elastase activity of the a,-macroglobulin (α,-M)-elastase complex was measured, and the relationship between these findings and the severity of pancreatitis was studied in 13 patients with pancreatic disease and 6 healthy subjects. When125I-labeled El was added to the sera of healthy subjects, it bound to α2-M and α1-protease inhibitor (α1-PI) with a mean ratio of 72:28. In mild acute pancreatitis (n = 9, the binding capacity of α2-M was less than that in healthy subjects. In severe pancreatitis (n = 4), most of the exogenous El bound to α1-PI (α2-M vs. (α2-PI, 13237). This diminution in the binding capacity of α2-M correlated well with the severity of acute pancreatitis. In the sera of patients (n = 4) with pancreatic cancer containing much immunoreactive El, the proportion of exogenous El bound by α2-M and α2PI (25:75) was similar to that seen in severe acute pancreatitis. A significant inverse relationship between the binding capacity of α2-M and the activity of the endogenous elastase bound to α2-M was seen in various pancreatic diseases. These findings suggest that in acute pancreatitis, the decreased binding capacity of serum α2-M and the increased enzymatic activity of the α2-M-protease complex correlate with the severity of the pancreatitis. In pancreatic cancer, however, this is not necessarily the case.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The exocrine pancreas was long thought to be composed of identical subunits, the acinar cells that store the inactive forms of the digestive enzymes in zymogen granules (ZGs). These were generally seen as a homogeneous population of vesicles. This homogeneity was recently questioned: Digestive demands are answered by the release of specific enzymes and immunocytochemical labeling showed distinctive nonidentical populations of ZGs. We have aimed at finding concomitant differences in element contents. We analyzed by energy-dispersive x-ray microanalysis (EDX) the subcellular distribution of elements in acinar cells of resting and stimulated rat, resting mouse, and resting pig pancreas and compared the results with values from the literature. We found large variances in the concentrations of Na, Mg, P, S, Cl, K, and Ca in cytoplasm rich in endoplasmic reticulum (C/E), whereas the concentrations of P, C1, K, and Ca in mitochondria and ZGs had surprisingly small variations. Na and Mg were detected in measurable amounts only in C/E and mitochondria and Ca was detectable only in ZGs. We could not find any other elements. We have not found clearly distinguishable populations of ZGs. We critically discuss our findings in comparison with the literature. Many discrepancies can be explained by the different preparation procedures. We show that it is questionable to present absolute values of concentration in biological specimens on the basis of EDX. The technique should, in our opinion, be used only for the study of relative concentrations.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID