摘要:

This study used a cholecystokinin (CCK) antagonist to evaluate whether CCK that is released after regular meals regulates meal-stimulated insulin secretion. Several experiments were performed in eight to 10 healthy male volunteers, each in duplicate. The subjects received different meals either with or without i.v. infusion of 5 mg/kg/h of the CCK antagonist loxiglumide (Rotta, Italy). The mixed solid-liquid meals of 600, 800, or 1,000 kcal consisting of regular German food were given orally. In addition, studies were carried out in which a liquid test meal of 750 kcal was infused into the duodenum over a 2-hour period to exclude effects of the CCK antagonist on gastric emptying. Finally, the subjects received an oral load of 100 g glucose either with or without i.v. infusion of loxiglumide. Loxiglumide at the dose used completely abolishes the actions of endogenous CCK and of exogenous CCK when given at doses that mimic postprandial circulating concentrations of this peptide at various target organs such as gallbladder, pancreas, stomach, and intestine. Loxiglumide also markedly reduced the increase in pancreatic polypeptide seen after the intraduodenal infusion of nutrients. However, loxiglumide at this dose did not alter the increase in circulating concentrations of glucose, insulin, and C-peptide after any of the various oral meals, after the intraduodenal administration of nutrients, and after the oral load of glucose. Although the present study does not rule out that in some conditions CCK may increase insulin secretion in humans, the results do rule out that CCK acts as a major physiologic incretin in healthy humans.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To clarify whether elemental changes are present before the onset of diabetes, freeze-dried pancreas sections from young (18–19 days-old), genetically prediabetic Chinese hamsters were subjected to proton bombardment and the concentrations of 15 elements (Na, Mg, Al, P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Rb, Cd, and Pb) in B cells and exocrine pancreas were calculated from the x-rays emitted. We have previously shown that islet B cells and exocrine pancreas from adult, overtly diabetic Chinese hamsters contain subnormal levels of Al (−61%, −88%) and excess levels of Cu (+ 92%, +59%), Rb (+13%, +13%), and Mg (+ 6%, +6%) in B cells and exocrine pancreas, respectively (Juntti-Berggren et al.,Biosci Rep1976;7:3341). In the present study the prediabetic B cells contained normal levels of all 15 elements, whereas the prediabetic exocrine pancreas contained a subnormal level of Fe (−10%; p <0.005). Hence, the development of diabetes in the Chinese hamster does not seem to be associated with an early change in the elemental composition of the pancreatic B cells. In fact, the overt diabetic condition may cause changes in the body's handling of some elements.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Oral cholestyramine, a bile salt sequestrant, stimulates pancreatic exocrine secretion and growth chiefly by increasing cholecystokinin (CCK) release. In this report, we examine pancreatic insulin content and insulin release from the isolated perfused pancreas in rats given oral cholestyramine (4%, wt/wt) or subcutaneous CCK-8 (1 μg/kg every 8 h) for 2 weeks. Cholestyramine significantly increased pancreatic weight by 32%. CCK administration significantly increased pancreatic weight by 15%. Total pancreatic content of protein and DNA were also increased significantly by cholestyramine and pancreatic protein content was increased significantly by CCK administration. Total pancreatic insulin content was not affected by cholestyramine or CCK. Both cholestyramine and CCK significantly increased the first phase of glucose (8.4 mM)-stimulated release of insulin [mean insulin output (ng/min): control, 2.0 ± 0.1; cholestyramine, 2.7 ± 0.2; CCK, 2.6 ± 0.23. Cholestyramine also significantly enhanced the second phase of glucose-stimulated release of insulin. Insulin release stimulated by CCK-8 (10−10M) was not affected by oral cholestyramine or CCK treatment. These findings indicate that oral cholestyramine and exogenous CCK have a stimulatory effect on B cell function. Since pancreatic insulin content was not affected by cholestyramine and CCK treatment, cholestyramine and CCK may increase the sensitivity of p cells to glucose. The absence of a stimulatory effect of cholestyramine and CCK administration on insulin release in response to CCK-8 may be related to a down-regulation of CCK receptors on β cells.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Pancreatic hypoplasia is an uncommon developmental defect that has not been well documented in association with type I diabetes mellitus. We report the case of a patient with an atypical clinical onset of type I diabetes mellitus who died following pancreas transplantation. Autopsy showed the surprising finding of hypoplasia of the native pancreas with other features indicating the concurrence of type I diabetes mellitus. These findings lead to speculation about the occurrence and interaction of these two diseases in our patient.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The cellular sequence of intraislet vascular perfusion has been shown to be important in the regulation of islet hormone secretion in the rat and dog islet. In order to test whether a B to A to D sequence of islet cellular perfusion is also present in a nonhuman primate, pancreata from the rhesus monkey,Macaca mulatta, were isolated and perfused in vitro in the presence and absence of anti-insulin gamma globulin. In the presence of the insulin antibody, efflux concentration of insulin decreased rapidly (−95 ± 1.8%), whereas glucagon and somatostatin concentrations increased (111 ± 28% and 239 ± 38%, respectively). These results suggest the presence of a B-A-D cellular sequence of vascular perfusion within the monkey islet. The present results also strongly support the hypothesis that a B-A-D sequence of islet perfusion is important in the regulation of islet hormone secretion and further emphasize the central role of the B-cell in intraislet cellular interactions. The results also suggest that, despite differences in islet anatomy, a B-A-D order of islet cellular perfusion may be the preferred functional sequence among mammalian species.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study was designed to investigate the effect of total gastrectomy on remnant islet cell function after 85% distal pancreatectomy in rats. Eight-week-old Wistar male rats were divided into the following three groups: group 1, laparotomy; group 2, distal pancreatectomy; and group 3, distal pancreatectomy with total gastrectomy. Four weeks after the operation, i.v. glucose tolerance tests (ivGTT) were performed. The body weight in group 3 rats 4 weeks after the operation was significantly lower than that of the other two groups (p <0.05). Glucose tolerance was impaired in both groups 2 and 3; group 3 was more impaired than group 2. Immunoreactive insulin (IRI) concentration in both groups 2 and 3 was much lower than that in group 1 throughout the ivGTT. Furthermore, IRI concentration in group 3 was lower than group 2 at all times. The integrated secretion of insulin for the 45 minutes after glucose injection was lower in group 3 than in group 2. It is concluded that total gastrectomy injures remnant pancreatic endocrine function after 85% distal pancreatectomy in rats.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Protein kinase C was purified 6,900-fold from rabbit pancreas with a total yield of 15% by a procedure involving ammonium sulfate fractionation, diethyl aminoethyl ion exchange chromatography, hydroxylapatite chromatography, and finally protamine-agarose affinity chromatography. After these purification steps the protein kinase C preparation contained two major protein bands as judged by silver staining after SDS-polyacrylamide gel electrophoresis: 80 and 69-kDa bands. Monoclonal antibodies directed against bovine brain protein kinase C (a- and p-subtype) recognized only the 80-kDa band. On the other hand, both the 80 and 69-kDa proteins were recognized by a polyclonal monospecific antibody directed against rat brain protein kinase C. Analysis of rabbit pancreas protein kinase C subtypes by means of hydroxylapatite chromatography showed the presence of the III (a) subtype as the major subtype. The enzyme depended absolutely on the presence of both phosphatidylserine and Ca2+for its activity, with apparent K, values of 3.1 μg/ml and 247 μM for phosphatidylserine and Ca2+, respectively. When dioctanoylglycerol or the phorbol ester 12-0-tetradecanoyl-phorbol 13 acetate (TPA) was present, the K, value for Ca2+decreased to 10 and 18 μM, respectively. In the presence of the phorbol ester, pancreatic protein kinase C could be activated without added Ca2+. The enzyme also required Mg2+for its activity. The K, value was 3.6 μM and maximal activity was reached at 10 μM Mg2+. Pancreatic protein kinase C activity showed a broad pH dependence, with optimal activity at pH 6.75. The K, value for ATP and for histone-HI was 8.5 μM and 20.4 μg/ml, respectively. The present study shows that the kinetic properties of protein kinase C purified from rabbit pancreas closely resemble those found in other tissues.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A modified procedure for the purification of ovine pancreatic lipase (triacylglycerol acyl-hydrolase, EC3.1.1.3) is described. The method is more rapid and more reproducible than that reported previously and results in a pure lipase preparation, that gives a better yield at the same specific activity, free of colipase and uncontaminated by lipid. The procedure involves the preparation of a lipid-free acetone powder from fresh pancreas without the use of chloroform or butanol as was used in the procedure described earlier. The aqueous purification of the lipase from the delipidated powder is similar to that described earlier, but includes the use of P-mercaptoethanol and uses salt gradient elution from CM-Sepharose. An assay procedure for lipase is reported involving the extraction of released free fatty acids with chlorofodmethanol before titrating with sodium hydroxide. A modification of this assay is used for the determination of colipase. The above assay procedure is compared to the potentiometric method reported previously. Polyacrylamide gel, amino acid composition analysis and N-terminal sequence data for the purified ovine lipase are presented.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In a comparative study of tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) occumng in the same population, we analyzed the clinical profile of 50 patients of ACP seen over the past 3 years at our centers and compared this with the profile of our TCP patients. A majority (75%) of patients in both groups belonged to Tamil Nadu and 90% had never consumed cassava. Whereas TCP occurred in young subjects of both sexes, ACP patients were all males and presented at an older age. The frequency of pain, diabetes, and pancreatic calcification was similar in the two groups. Patients in both groups were lean, but signs of severe malnutrition were rare. Prediabetic patients had normal body mass index. There were striking differences in radiological appearance of pancreatic calculi in TCP and ACP. Malignancy of the pancreas was present in three patients with TCP. Benign bile duct stenosis was seen in three patients with ACP but not in TCP. Compared to ACP seen in the West, our ACP patients had a shorter duration of symptoms in spite of having advanced disease. TCP and ACP have distinct clinical profiles and it is possible that some environmental factors may hasten the progress of ACP in the tropics.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To investigate the mechanism of phospholipid hydrolysis in pancreatic acinar cells, the effects of Ca2+, guanosine 5′-O-(3-thiotriphosphate) (GTPγS) and cholecystokinin (CCK) on both polyphosphoinositide (PI) and phosphatidylcholine (PC) hydrolysis were studied in rat pancreatic acini per-meabilized with the bacterial toxin, streptolysin-O. When acini were prela-beled with my∼-[3H]inositol, permeabilized, and then incubated with various concentrations of free Ca2+for 15 min, Ca2+stimulated [3H]inositol phosphate release at a concentration of 100 nMand was maximally effective at 100 μM. Both GTPγS and CCK enhanced Ca2+-induced [3H]inositol phosphate release, although these agents had no effect in the absence of Ca2+. At a physiological concentration of Ca2+(100 nM), CCK stimulated [3H]inositol phosphate release which was further enhanced by GTPγS. When acini were similarly prelabeled with [3H]choline before permeabilization, [3H]choline phosphate release was also stimulated by free Ca2+over the concentration range from 100 nMto 10 μM. In contrast to PI hydrolysis, however, neither GTPγS, CCK, or GTPγS plus CCK had an additional effect on [3H]choline phosphate release stimulated by 100 nM-100 μM free Ca2+. Furthermore, Ca2+-induced [3H]choline phosphate release appeared to be due to the redistribution from cell to the medium rather than to an increase in choline phosphate production. Therefore, choline phosphate release following prelabeling with [3H]choline is not useful as an indicator of PC hydrolysis in permeabilized acini.

ISSN:0885-3177    

出版商:OVID    

年代:1992

数据来源: OVID