摘要:

Insulin flux was determined in the portal vein and simultaneously arterial blood glucose was measured before and during an oral glucose meal in conscious normal and pancreatic islet cell-autotransplanted dogs to test their insulinogenic reserve. These dogs had previously been chronically instrumented with blood flow probes on the portal vein and carotid artery, and blood sampling catheters in the portal vein, hepatic vein, carotid artery, and right external jugular vein. Such a model permits quantitative portal-peripheral comparisons and assessment of hepatic extraction. Sixteen dogs, 10 normal (N) and six long-term (2 months to 2 yrs) islet cell-transplanted dogs (IT) were fed an oral glucose meal as a test (OMT). Baseline portal vein insulin fluxes (PVF) were similar in both groups (25.6 2 0.04 pmol/min in N and 24.7 k 19.4 pmol/min in IT). Immediately after OMT, PVF rose to 248.2 2 40.9 pmol/min in N, but only to 55.9 ± 17.9 pmol/min in IT. After 30 min PVF peaked for the second time in N at 156 k 35.9 pmol/min, declining slowly to baseline after 3 h. In IT, a similar peak at 30 min was seen (143.7 ± 22.1 pmol/min), declining to a value not different from baseline after 3 h. However, cumulative insulin PV fluxes in the two groups over 3 h were not different. Differences were also seen in postprandial glucose fluctuations, which reached a maximum excursion of 11.8 ± 0.45 mM in IT, while never rising above 7.8 t 0.33 mM in N. After 3 h both groups had similar glucose values. The principal defect discerned in IT was the lack of adequate first-phase insulin secretory response to OMT. Consequently, whereas islet cell-transplanted dogs were able to maintain fasting blood glucose within a normal range, the postprandial glucose responses showed greater fluctuations than normal.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Insulin release and45Ca2+uptake were studied in isolated islets from Chinese hamsters of genetically diabetic and normal sublines. The calcium channel agonist, perchlorate (C104-, 12 mmol/L), augmented both45Ca2+uptake and insulin release from normal islets in the presence of 20 but not 1 mmol/L glucose. The agonist also amplified the glucose-stimulated45Ca2+uptake and insulin release from diabetic islets but did not normalize the insulin release despite normal insulin concentration in the diabetic Chinese hamster islets. The dry weight of the diabetic islets was subnormal (54%,p< 0.005) but the insulin concentration (insulin per dry weight of islet tissue) was not different from normal (122%). It appears that there are defective mechanisms in addition to the glucose-stimulated influx of Ca2+in diabetic islet B cells.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The functional state of the p cells has been suggested to play a pathogenic role in IDDM by altering p-cell autoantigen expression. In this study, we investigated expression of GAD-65 and GAD-67 in isolated Sprague-Dawley rat islets cultured at different glucose concentrations. Using GAD isoform-specific antibodies in an immunoblot assay, we found that expression of both GAD-65 and GAD-67 in cultured islets was glucose dependent and that increased expression of both forms of GAD correlated with increased functional state of the β cell. Our data indicate that the functional state of the β cell influences islet cell expression of GAD. Thus, decreasing islet cell expression of GAD by suppressing β cells activity may have a potential role in blunting the autoimmune destruction of pancreatic islet p cells.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Pancreatic acinar cells within the islets of Langerhans in human pancreas were investigated both histopathologically and electron microscopically. Acinar cells inside the islets of Langerhans were observed in all 50 adult cases investigated. Between such acinar cells and endocrine tissues, no reticular fiber was observed; they were encapsulated together instead. The acinar cells were immunostained with antiamylase similar to the “extrainsular” acinar cells and were also connected to the small pancreatic duct. Electron microscopically, intercellular junctions of the desmosomal type were found between the acinar cells and the adjacent endocrine cells. Therefore, the acinar cells within the islets of Langerhans were true acinar cells, based on the incomplete demarcation between the islets and the acinar tissue.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Endocrine cells of the pancreatic and bile duct system of the diabetic rat were characterized with reference to their influence on duct function. In streptozotocin-induced diabetic rats, the endocrine cells showed various changes in number and topographic distribution along the epithelial lining of the duct system. With the exception of insulin cells, which demonstrated a marked decrease, the number of duct endocrine cells generally increased in the duct system of the diabetic animal, particularly in the terminal portion of both the common hepatic and the accessory pancreatic ducts encompassed by the muscle sphincters. Among them, the cells secreting somatostatin, a potential peptide inducing contraction of the muscle sphincter, showed a remarkable increase in the opening portion of the common hepatic and the accessory pancreatic ducts of the diabetic animal. The duct cells producing glucagon and pancreatic polypeptide, the hormones exerting an inhibitory effect on exocrine secretion of duct and acinar cells, also increased significantly in the duct system of the diabetic animal. These results suggest that the duct endocrine cells are closely related, not only to functional properties of the duct system, but also to disorders of the pancreas and biliary tract in diabetes.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To clarify the role of nitric oxide (NO) in the pancreas, blood flow in the rat pancreas (pancreatic blood flow: PBF) was investigated by the hydrogen clearance technique using a specific NO synthase inhibitor, Nω-nitro-L-arginine (L-NNA). Continuous infusion of caerulein at doses of 5 and 20 μg/kg/h caused a significant increase in PBF in the early phase of caerulein infusion. The caerulein-induced increase in PBF was not affected significantly by atropine sulfate (100 μg/kg), nor by phe-noxybenzamine (5 mg/kg) plus propranolol (50 μg/kg). Administration of L-NNA (0.5, 5, or 30 mg/kg) did not affect the basal PBF, but at 5 mg/kg it inhibited completely the caerulein-induced increase in PBF. The inhibitory action of L-NNA was reversed by a large dose of L-arginine (100 mg/kg bolus, i.v., followed by a continuous infusion at 400 mglkglh), but not by its enantiomer D-arginine. These results strongly suggest that NO has a mediator role in the early phase vascular response of the pancreas to superphysiologic doses of caerulein.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Fecal bile acid and fecal fat were determined in 18 normal subjects and 22 patients with chronic pancreatitis, and the relation of fecal bile acid excretion to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal bile acid was approximately three times that of control subjects, and large amounts of primary bile acid were detected. A significant correlation between fecal bile acid excretion and bicarbonate secreted from the pancreas was found. This evidence of bile acid malabsorption was not observed until bicarbonate output was ∼0.05 mEq/h/kg. A slight correlation between fecal bile acid and absorption rates of fat was demonstrated. These results suggest that bile acid malabsorption observed in chronic pancreatitis is related to an impairment of pancreatic bicarbonate secretion.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The mechanisms of the stimulatory effect of the bombesin-like peptide neuromedin C on pancreatic exocrine secretion were examined in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. Intravenous infusion of 0.35 nmol/kg/h of neuromedin C significantly increased the secretions of pancreatic bicarbonate and protein, and transiently increased the plasma cholecystokinin (CCK) concentration. The increase in pancreatic secretion persisted for 90 min, whereas the increase in plasma CCK was observed only after 15 and 30 min from the beginning of neuromedin C infusion. Intravenous infusion of CR-1409, a specific CCK-receptor antagonist, inhibited, but did not abolish, the protein secretion stimulated by neuromedin C. Intraduodenal infusion of a potent proton pump inhibitor, omeprazole, suppressed, but did not abolish, protein secretion induced by neuromedin C. Omeprazole abolished the increase in bicarbonate secretion produced by neuromedin C. These results indicate that neuromedin C induces release of CCK and that its induction of pancreatic hypersecretion is due to both its direct effect and CCK. The results also suggest that gastric hypersecretion may have a role in the bicarbonate hypersecretion induced by neuromedin C.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Inositol 1,4,5-trisphosphate (InsP3) is an intra-cellular second messenger, produced upon stimulation of the phosphoinositide system, capable of mobilizing calcium from intracellular stores. The properties of InsP3receptor sites in the rat pancreas were evaluated by binding studies with InsP3labeled with3H. Specific binding was very sensitive to pH variations between 7 and 9. Kinetic studies showed that specific binding of InsP3at 0°C was half-maximal in about 10 min and reached a plateau within 60 min with aK+, = 3.37 × 109mol−1min−1. Binding was reversible as addition of 10−6Munlabeled InsP3was followed by dissociation of the bound ligand with aK-1, = 0.016 min−1. Scatchard analysis of the binding data was consistent with a single set of high-affinity sites withKDof 9.9 ± 2.47 nMand a maximal binding capacity of 210 ± 55 fmol/mg of protein (n= 7). The specificity of [3H]InsP3binding to these sites was illustrated by the much weaker affinity for structural analogs such as inositol 1,3,4,5-tetrakisphosphate, phytic acid, fructose 1,6-bisphosphate, and heparin. To assess the functional relevance of the InsP3binding sites, the Ca+-releasing activity of InsP3was measured in perme-abilized acinar cell preparations. In the presence of oli-gomycin (10 μg/ml), Ca2+movements were monitored with the fluorescent indicator fura-2 (free acid). Under these conditions, 4 mM ATP caused rapid uptake of Ca2+by the vesicular component of the acinar cells. Addition of InsP3(0.1-15 pA4) caused a dose-dependent release of Ca2+with half-maximal effect at 3.2 pM. Finally, the calcium release by InsP3showed a positive cooperativity with a Hill coefficient of 1.53. Under physiologic conditions within the cytosol, the high-affinity InsP3binding sites characterized in the rat pancreas membranes serve as a receptor through which InsP3triggers Ca2+mobilization for secretion process stimulated by cholecystoki-nin and/or acetylcholine.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We have studied the effects of acetylcholine (ACh), and other agents that modulate pancreatic bicarbonate secretion, on the anion permeability of a human ductal adenocarcinoma cell line (BxPC-3). Anion permeability was monitored using an125I efflux assay. ACh (10 μM) markedly stimulated125I efflux from BxPC-3 cells and this response was abolished by atropine (10μM), indicating that it is mediated by muscarinic receptors. Using transport inhibitors and ionophores, we obtained data indicating that some of the ACh-induced125I efflux results from the opening of K+channels, which would hyperpolarise the cell and increase the electrical driving force forlzSl exit. The remaining ACh-induced125I efflux is not mediated by anion exchangers or by Na+/KC/2C1-cotransporters, and is probably explained by activation of an anion channel in the BxPC-3 cell membrane. Ionomy-cin (0.5 pkf) caused a small rise in125I efflux, indicating that this process can be triggered by an increase in intra-cellular calcium concentration. ATP (100 μM), ADP (100 μM), bombesin (10 μM), and cholecystokinin (CCK) (10 μM) also stimulated125I efflux, indicating that receptors for these agents are expressed on BxPC-3 cells. We speculate that bicarbonate secretion from the human pancreas could be modulated by ACh, ATP, bombesin, and CCK via a direct effect on the duct cell.

ISSN:0885-3177    

出版商:OVID    

年代:1994

数据来源: OVID