ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Synthesis-secretion coupling of insulin was determined in perfused pancreases stimulated for 3 h by various sugars. These monosaccharide stimuli included glucose alone at either 200 or 300 mg/dl; mannose or fructose alone at 1,200 mg/dl; or combinations of mannose and fructose or galactose and fructose at 600 mg/dl each. Glucose and mannose each promoted insulin synthesis and secretion. Mannose at 1,200 mg/dl produced synthesis-secretion coupling similar to glucose at 200 mg/dl. Fructose alone at 1,200 mg/dl failed to cause any significant release of insulin, but it did significantly increase beta cell insulin content. When mannose and fructose were combined at 600 mg/dl each, in the absence of glucose, they resulted in a synergistic effect on insulin secretion and an additive effect on insulinogenesis, which was in excess of, or equal to, the insulinotropic effect of glucose at 300 mg/dl. These results clearly establish that the synthesis and secretion of insulin can be uncoupled. Mannose primarily stimulates the putative beta cell glucoreceptor, and fructose signals the insulin biosynthetic pathway. When combined, these monosaccharides couple synthesis-secretion of insulin comparable to glucose. The data suggest that the uncoupling of insulin secretion and synthesis, which may contribute either independently or in combination to abnormalities in pancreatic function observed in various diabetic conditions can be studied using the isolated perfused pancreas model. Use of this relatively physiological experimental model should provide optimal opportunity to further investigate and identify cellular controlling signals regulating either insulin biosynthesis, insulin secretion, or the coupling of both mechanisms.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Islet vasculature was studied in rats rendered dietarily copper-deficient, a regimen that effects progressive acinar atrophy while leaving islets and ducts intact. Scanning electron microscopy of corrosion casts produced from Mercox injected rats was used to analyze islet angioarchitecture in the atrophied gland. The results indicate that with the onset of acinar atrophy, the vasculature of islets remained intact despite loss of insuloacinar interconnectivity. With atrophy of the dense acinar vascular matrix, three populations of islets could be distinguished according to their size and vascular structures: (a) All small islets (40–150 pm in diameter) were found to have exclusively serial vasculature since no postcapillary collecting venules were found directly continuous with parallel efferent veins. (b) A second population of intermediate size islets (160–250 pm) was found to have serial vessels in addition to post- capillary collecting venules that were directly continuous with larger interlobular veins indicative of a parallel mode of microcirculation. (c) All larger islets (26&700 pm) were also found to have both serial as well as parallel microcirculatory patterns based upon the coexistence of both types of postcapillary venules within the same islet. In all cases, postcapillary venules, which normally link islet capillaries to peri-insular acinar plexuses, were continuous with veins that extended through lipomatous lobules devoid of acini to link with branches of interlobular veins. It is proposed that the functional integrity of islet blood flow remains in the atrophied pancreas because of preservation of both serial and parallel microcirculation that facilitate normal glucose- stimulated insulin secretion in the atrophied pancreas, as demonstrated in an earlier study. Furthermore, it is suggested that analysis of the atrophied state of the gland provides a valid comparative model with which to study islet angioarchitecture and microcirculation in the normal gland.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The presence of pancreatic juice in the intestinal lumen results in the hydrolysis of dietary fat. The hydrolytic products of dietary fat are potent stimulants of pancreatic exocrine secretion and potent inhibitors of gastric acid secretion. In this study, residual pancreatic enzyme activity in the intestinal lumen may account for the observed increase of triglyceride-stimulated pancreatic exocrine secretion and the release of peptides during diversion of pancreatic juice. The presence of pancreatic juice enhanced the pancreatic protein output that was stimulated by the intraduodenal administration of a triglyceride (corn oil, 2 g/kg/h) by 240% (p < .05). The presence of pancreatic juice during the intraduodenal administration of a triglyceride nearly abolished the output of gastric acid as well as the release of gastrin (p < .05) that had been stimulated by the intragastric placement of a 10% peptone meal. Pancreatic juice in the duodenum significantly enhanced the triglyceride-stimulated release of cholecystokinin-33/39, secretin, neurotensin, peptide YY, pancreatic polypeptide, and insulin (p < .05) when compared with the release of these entero-pancreatic hormones during the diversion of pancreatic juice. This study shows that the presence of pancreatic juice in the duodenal lumen enhances the fat- stimulated release of enteric hormones that have a stimulatory action on the enteroacinar and enteroinsular axis as well as an inhibitory action (enterogastrone-like activity) on the postprandial regulation of gastric function.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We examined the effects of cellophane wrapping of the pancreas on the age-related uptake of tritiated thymidine (3H-TdR) by the differentiated cell types of the pancreas of the Syrian golden hamster. Fifty-two hamsters were studied. At 7 weeks of age, hamsters underwent cellophane wrapping (n = 32) or were allocated to a control group (n = 20). Animals 8–22 weeks of age (four at each interval) received3H-TdR (2 μCi/g) intraperitoneally and were killed 1 h later. Pancreatic tissues from each animal was processed for autoradiography. The percent of acinar cells labeled with3H-TdR at 8 weeks, in control and wrapped animals, was 1.17 ± 0.26 and 1.51 ± 0.38 respectively (p = N.S.). In control animals, this steadily diminished to 0.02 ± 0.00 at 22 weeks. In wrapped animals, there was less of a tendency for acinar cell labeling to decrease with age, and the percent of labeled acinar cells in wrapped animals at 22 weeks was 0.05 ± 0.00. The percent of ductular cells labeled with3H-TdR at 8 weeks in control and wrapped animals was 0.24 ± 0.24 and 0.98 ± 0.24, respectively (p = N.S.), and at 22 weeks was 0.13 ± 0.90 and 0.60 ± 0.03, respectively (p < 0.01). The percent of islet cells labeled with3H-TdR at 8 weeks in control and wrapped animals was 0.16 ± 0.01 and 0.42 ± 0.01, respectively (p < 0.05), and at 22 weeks was 0.18 ± 0.01 and 0.63 ± 0.05 (p < 0.05), respectively. In the major ducts in the head of the gland, the number of epithelial cells per millimeter duct length that were labeled with3H-TdR in control animals was stable throughout the study: 3.25 ± 1.5 at 8 weeks and 3.35 ± 1.3 at 22 weeks. In the wrapped group, the number of labeled duct epithelial cells was greatest at 8 weeks (22.5 ± 7.5) and then declined to 13.7 ± 4.5 at 12 weeks, at which time it stabilized. It is concluded that cellophane wrapping of the pancreas is a mitogenic stimulus that affects all cell types in the pancreas of the Syrian golden hamster. The greatest trophic affect was on cellular elements of the ductal system and on islet cells.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), inhibits growth of some cancers. a-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. We and others have previously shown that DFMO inhibits cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on the growth of H2T hamster pancreatic ductal adenocarcinoma. Twenty-eight male Syrian golden hamsters were inoculated with 500,000 H2T cells, and then randomized into four groups of seven each: group 1 served as control; group 2 received DFMO (3% in drinking water); group 3 received 2-DG (500 mg/kg/day) intraperitoneally; group 4 received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation and continued for 28 days. At the end of the treatment period, the area of the H2T tumor was reduced 31% by DFMO compared with a 22% reduction caused by 2-DG. Tumor weight was significantly reduced (31%) by DFMO but not by 2-DG. Tumor contents of DNA, RNA, and protein were also reduced by DFMO but not 2-DG. Tumor concentration of the polyamines, putrescine and spermidine, were reduced by DFMO, but 2-DG did not alter levels of polyamines. The combination of DFMO and 2-DG caused a significantly greater reduction in tumor weight and putrescine content compared with DFMO alone. These results indicate that DFMO is capable of inhibiting pancreatic cancer growth in vivo and that this inhibition is potentiated by the addition of the glucose antimetabolite 2-DG, although 2-DG alone has no antitumor effect. Further study of 2-DG and DFMO may provide information of therapeutic value.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Pancreas-specific protein (PASP) is a recently isolated and partially characterized major protein in the human pancreas. It has not been described previously. Serum levels of PASP and amylase were analyzed in 21 patients subjected to combined renal and segmental pancreatic transplantation with both organs obtained from the same donor and in eight kidney transplant patients. In the pancreas transplant patients, PASP and amylase levels were elevated in episodes of graft pancreatitis. With chronic graft rejection, PASP rose to high levels long before other indications. In episodes of renal rejection, the levels of PASP, but not always of amylase, were elevated on several occasions. They decreased after antirejection therapy. This may indicate accompanying pancreatic graft rejection. PASP and amylase levels were stable in kidney transplant patients and were not affected by serum creatinine levels, renal rejection, or antirejection therapy. The results support earlier observations that renal rejection in combined pancreas and renal transplant patients may or may not be accompanied by a rejection process in the pancreatic graft. PASP may be the means by which to tell when the pancreatic graft is involved.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

It was recently proposed that the role for poly(ADP-ribose) synthetase during DNA repair was exerted via a depletion of cellular NAD in order to slow down energy-requiring processes in the cell, notably DNA replication. This would enable the cell to more efficiently repair damaged DNA. In the present study fetal rat pancreatic islet cells were exposed to 2.2 mM streptozotocin (SZ). Using [3H]thymidine labeling and autoradiographic techniques, it was found that cellular nuclear silver grain counts, an index of DNA repair synthesis, were doubled after SZ exposure. However, autoradiographically measured DNA replication remained unaffected. Cellular NAD + NADH contents were reduced by 60% in the SZ-treated islets. Estimates of the poly(ADP-ribose) synthetase activity showed that this was doubled in islets exposed to SZ. Immediately after the SZ treatment the islets exhibited a 35% reduction in insulin secretion in response to 16.7 mM glucose. Taken together, the present findings do not favor the suggested role for poly(ADP-ribose) synthetase during DNA repair. Rather we observed an increased activity of this enzyme, a lowered cellular NAD + NADH content, and an increased rate of DNA repair synthesis concomitant with an unchanged DNA replicative rate in the SZ-exposed islets.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effects of sodium butyrate, a differentiating agent, on growth properties and glycoconjugates of a human pancreatic carcinoma cell line (CAPAN-1) were studied. Butyrate caused marked changes of in vitro growth properties including prolongation of doubling time and greatly reduced colony forming efficiency in soft agar. Cell surface labeling revealed significant alterations in proteins and glycoproteins after treatment with sodium butyrate (appearance of glycoproteins of molecular weight 250,000, 220,000, and 70,000; reduction of glycoproteins of 164,000, 148,000, 110,000, and 66,800 sizes; increases in proteins/glycoproteins of 85,000 and 78,000). Metabolic labeling of the cells with [3H]fucose or [3H]galactose revealed that sodium butyrate treatment caused a marked reduction in the fucose-containing neutral glycolipids with six or more carbohydrate side chains and an increase in [3H]galactose-labeled neutral glycolipids, particularly GL-3a, GL-4a, and GL-Sa. There was marked reduction in the labeling of a ganglioside with mobility similar to that of GM4and of sulfogalactosylceramide. An increase in a ganglioside with mobility above GM, was also caused by butyrate. These data indicate that sodium butyrate may be useful in the identification of differentiation or malignancy-associated glycoconjugate markers of human pancreatic cells.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

To investigate diabetic alterations of small intestinal transit and bacterial growth, we performed hydrogen breath tests (10 g lactulose via duodenal tube at the ligament of Treitz), bacterial cultures, and determinations of unconjugated serum bile acids in 19 patients with long-standing diabetes and 7 healthy controls. Asymptomatic diabetics had a late rise in breath hydrogen, indicating prolonged jejunal-cecal transit (86 ± 10 min, p < 0.05) as an early pathogenic event. Rise in breath hydrogen in symptomatic diabetics (constipation: 50 ± 6 min; diarrhea: 41 ± 11 min) was not significantly different from controls (57 ± 8 min). Bacterial studies and increased unconjugated serum bile acids suggest bacterial overgrowth in some symptomatic diabetics. Bacterial overgrowth was associated more frequently (p < 0.05) with a rise in breath hydrogen before 45 min or after 75 min. Changes in the hydrogen breath test, bacterial growth, or unconjugated serum bile acids did not correlate with gastrointestinal symptoms of diabetes.

ISSN:0885-3177    

出版商:OVID    

年代:1989

数据来源: OVID