摘要:

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin- dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NIDDMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white Caucasians from the U.K. of 140–414 μg/L), pancreatic isoamylase (PIA, normal of 35–125 U/L), and fecal chymotrypsin (FCT, normal of >6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT >800 μg/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 μg/L (range of 102–1,360 μg/L), FCT of 2.2 u/g (range 0.7–12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 pg/L (range of 30–1,360 μg/L), FCT of 4.2 u/g (range of 1–38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 μg/L (range of CL184 μg/L), FCT of 0.23 u/g (range of 0–10.4 u/g)]; none showed IRT > 800 μg/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in ∼30 and ∼10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed “pancreatitic” IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls. Simultaneous measurements showed that IRT concentrations were reduced when PIA concentrations were still normal. Our results suggest that TCP and FCPD (diagnosed by radiographically demonstrable pancreatic calculi) represent advanced disease and that a subclinical “pancreatopathy” appears to be common in tropical subjects (diabetic as well as nondiabetic). Endocrine impairment (hyperglycemia) in TCP parallels exocrine damage.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present study describes the effects of growth hormone (GH), amino acids, and human amniotic fluid on the function and replication of normal and SZ-treated adult mouse pancreatic islets. Thus, mouse islets were exposed in vitro to SZ or vehicle only, and maintained in culture for 7 days in RPMI 1640 containing 11.1 mM glucose and the different supplements described above. Supplementation with amino acids increased the insulin accumulation in the medium, DNA biosynthesis, and polyamine contents in the control islets. In the SZ-treated islets, amino acids increased insulin accumulation in the medium and polyamine contents, but not DNA biosynthesis. Culture of control islets in the presence of 10% human amniotic fluid increased the insulin accumulation in the medium, islet insulin content, total protein and (pro)insulin biosynthesis, and DNA biosynthesis. However, in the SZ-treated islets, the effects of human amniotic fluid were limited to an increase in insulin content and insulin accumulation in the medium. GH significantly increased insulin accumulation in the medium in control, but not SZ-treated islets. In both groups of islets, GH failed to induce a signifcant increase in thymidine incorporation. It is concluded that amino acids and human amniotic fluid are potent stimulators of DNA biosynthesis in adult mouse pancreatic β cells, perhaps due to an increase in cellular polyamine contents. However, following exposure to streptozotocin, the islets are not anymore responsive to these stimulators of DNA biosynthesis.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We assessed the heterogeneity in the islet cell cytoplasmic antibody (ICA) response of insulin-dependent diabetes mellitus (IDDM) patients via indirect immunofluorescence on frozen sections of human, bovine, and porcine pancreas. The three substrates detected comparable frequencies of ICA positives among the IDDM sera tested, whereas control sera were ICA negative on all three substrates. However, individual IDDM serum samples showed heterogeneity in ICA binding on the three pancreata. Of 28 sera tested on all three substrates, 22 were ICA positive on human pancreas, three were ICA positive on bovine pancreas, and two were ICA positive on porcine pancreas. Sensitivity of ICA epitopes to neuraminidase treatment and periodate oxidation suggests that glycoconjugates are recognized by serum ICA. Cholera toxin blocked ICA binding. However, the functional cholera toxin receptor ganglioside Gml is resistant to neuraminidase treatment and periodate oxidation. Therefore, it is unlikely that Gml is the ICA determinant. These data suggest that not all ICA antigens are equivalently expressed on islets from different pancreata andlor that each individual responds to a hierarchy of islet antigens such that restricted patterns of specific ICA binding are found.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The purpose of the study was to examine the transhepatic and peripheral effects of somatostatin (SN) infusion on plasma glucose and insulin during insulin (IN) infusion. Hepatic blood flow was measured electromagnetically during intermittent sampling from the portal and hepatic veins, femoral artery, and right external jugular vein. Hepatic blood flow [sum of portal vein (PV) and hepatic artery] was similar during IN or IN + SN infusions. IN concentrations decreased in the portal vein from 374.8 ± 50.3 to 295.8 ± 25.9 pM (p < 0.01) when SN was infused with IN. Hepatic venous plasma IN concentration also decreased from 143.6 ± 26.6 to 88.3 ± 10.1 pM (p < 0.01). Plasma IN concentrations in the femoral artery and jugular vein remained unchanged. Hepatic insulin extraction changed from 64 ± 4% during IN to 72 ± 3% during IN + SN (p < 0.01). Hepatic clearance and total body clearance were unchanged. Peripheral venous glucose with a nadir of 3.82 ± 0.2 mM during IN alone decreased to a nadir of 3.16 ± 0.27 mM (p < 0.01) during IN + SN infusion. Mean portal venous glucose concentrations were 5.0 ± 0.27 and 3.4 ± 0.19 mM, respectively (p < 0.01). In two additional experiments in which endogenous C-peptide concentrations were examined in the portal vein and femoral artery, C-peptide levels were lower during IN + SN compared to IN alone. We conclude that SN used to suppress endogenous insulin secretion increases hepatic insulin extraction, lowers glucose concentrations, and suppresses endogenous C-peptide levels to a greater extent than insulin infusion alone. These effects must be considered if somatostatin is used pharmacologically to suppress endogenous insulin secretion.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The BBIW strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and >80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Stimulation of intact rat pancreatic acini with cholecystokinin (CCK) enhances the phosphorylation of the ribosomal protein S6 in a dosedependent manner with half maximal stimulation at 40 pM and maximal stimulation at 1 nM CCK octapeptide. Soluble cellular extracts contained S6 kinase activity assayed using purified rat pancreatic ribosomes as substrate. Stimulation by CCK of S6 kinase was concentration dependent, being half maximal at 50 pM and maximal at 1 nM CCK. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C, also increased both S6 phosphorylation in intact acini and soluble S6 kinase activity. In order to determine whether S6 kinase mediated S6 phosphorylation following CCK treatment of acini, two-dimensional phosphopeptide analysis was performed for S6 proteins phosphorylated under various conditions. These data suggest that a specific soluble S6 kinase, the activation of which appears to be directly or indirectly mediated by protein kinase C, is the functional enzyme in intact acini that mediates the action of CCK to increase S6 phosphorylation and may be involved in increased protein synthesis in pancreatic acini treated with CCK.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A bioassay for studying the cholecystokinin (CCK)-releasing activity of intraluminal protease-sensitive bioactive peptides was developed. In conscious rats, bile and pancreatic juice were chronically diverted from the proximal intestine to the ileum to cause chronic stimulation of CCK release and pancreatic protein secretion. CCK-releasing activity of test substances was assayed during transient inhibition of CCK release by intraduodenal sodium taurocholate (78 μmol/h). Intestinal secretion as a source of the putative trypsin-sensitive intestinal CCK-releasing peptide was obtained by rapid intestinal perfusion of isolated Thiry-Vella fistulae of jejunum in conscious rats, collected with or without atropine pretreatment. Partially purified rat pancreatic secretory trypsin inhibitor (PSTI, or “monitor peptide”) was compared with ovomucoid trypsin inhibitor (OMTI) and with concentrated jejunal secretions for CCK-releasing activity and trypsin inhibitor activity. Concentrated, heat-treated jejunal secretions were the strongest stimulants of CCK release and pancreatic protein secretion in this model. OMTI had no CCK-releasing activity in this model, whereas a larger amount (∼5x, based on trypsin inhibitor activity) of PSTI weakly but significantly stimulated CCK release. CCK releasing activity manifested by pancreatic protein secretion was equivalent in intestinal washes from atropine-treated and control Thiry-Vella fistula donor rats. Concentrated jejunal secretions had no trypsin inhibitory activity, indicating that the putative intestinal CCK-releasing peptide and “monitor peptide” are different substances.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We measured pancreatic enzyme and bicarbonate responses to graded doses of intravenous secretin or cerulein alone or together in healthy human subjects. Bicarbonate responses were steady and well maintained during the last 3.5 h of the 4 h of infusions of secretagogues, giving evidence for a constant pancreatic flow rate. Potentiation (more-than-additive response) was observed between secretin and cerulein for bicarbonate secretion, but not for enzyme secretion. Secretin stimulated pancreatic enzyme secretion. The effect was most pronounced with amylase secretion and less prominent with lipase, trypsin, and chymotrypsin secretion. Changes in the proportion of enzymes were seen over time, with trypsin and chymotrypsin output declining towards the end of cerulein infusion. We conclude that in humans the effects of secretin on pancreatic enzyme secretion are complex and include timedependent changes in the enzyme mixture, but potentiation between secretin and cerulein does not occur for enzyme output.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A 67-year-old woman was admitted to the hospital because of intermittent pain in the upper left quadrant of the abdomen. Ultrasound and computed tomography (CT) scan revealed a mass in the body of the pancreas, and angiography demonstrated encasement of the celiac trunk and splenic vein thrombosis. She was thought to have a pancreatic carcinoma and was surgically explored to obtain tissue for diagnosis. A hard and irregular tumor was found, and biopsies revealed granulomatous inflammation with caseous necrosis. The final diagnosis was tuberculosis, and treatment with rifampicin, isoniazid, and ethambutol was undertaken. One year later the patient is asymptomatic and new CT scan shows disappearance of the pancreatic mass.

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0885-3177    

出版商:OVID    

年代:1990

数据来源: OVID