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J M Conlon

Publications and source records attributed to J M Conlon.

At least 307 records · Page 17Linked to original sources
PubMed1985

Primary structure of glucagon and a partial sequence of oxyntomodulin (glucagon-37) from the guinea pig.

Two glucagon-like peptides have been isolated from guinea pig pancreas and their primary structures determined. A 29-residue peptide is identical to the glucagons from all other mammals yet studied in the N-terminal region (residues 1-20) but the C-terminal region [Gln-Phe-Leu-Lys-Trp-Leu-Leu-Asn-Val] contains five substitutions. A 37-residue peptide probably represents guinea pig glucagon extended from the C-terminus by [Lys-Arg-Asn-Arg-Asn-Asn-Ile-Ala] and is analogous to human oxyntomodulin (glucagon-37). The structures suggest evolutionary pressure to conserve the N-terminal region of glucagon and the C-terminal region of oxyntomodulin. The biological activity of guinea pig glucagon has not yet been determined but it is speculated that changes in the C-terminal region of glucagon may have produced a molecule with reduced biological potency that is appropriate to the reduced potency of guinea pig insulin.

Amino Acid Sequence↗
PubMed1985

Isolation of neuropeptide-containing vesicles from the guinea pig ileum.

Three distinct vesicle fractions enriched 40-60 times in the neuropeptides substance P, somatostatin, and vasoactive intestinal peptide (VIP) were prepared from the myenteric plexus of guinea pig ileum by density gradient centrifugation in a small zonal rotor. Mean densities (in g X ml-1) and diameters (in nm) of the three classes of vesicles were: substance P, 1.123, 65; somatostatin, 1.138, 37; VIP, 1.148, 110; standard deviations were about 5%. These peaks were distinct from the peak of acetylcholine-containing vesicles of density 1.066 g X ml-1 and diameter 61 nm. When a relatively mild method of homogenization was used a second peak of acetylcholine appeared in the same region of the gradient as VIP and the VIP was larger. This may represent a class of vesicles containing both acetylcholine and VIP, though cosedimentation of two classes of vesicles of almost the same density and similar fragility, one containing VIP and the other acetylcholine, cannot be entirely excluded on present evidence.

Acetylcholine↗
PubMed1985

The effect of pancreatic acinar atrophy upon the concentration of vasoactive intestinal polypeptide, substance P, somatostatin and glucagon in the pancreas and gastrointestinal tract of the rat.

Atrophy of the exocrine pancreas was induced in rats by feeding a copper-deficient diet combined with penicillamine. The treatment resulted in significant decreases in the weights of pancreas and stomach but an increase in the weight of the small intestine compared with control animals receiving the same amount of food. Despite almost total destruction of acinar cells, the content of vasoactive intestinal polypeptide, (VIP) and substance P in the pancreas was not different from controls but the total somatostatin increased by 258% and the glucagon content by 370%. Significant decreases (p less than 0.05) in the concentrations (pmol/g) of VIP, substance P and somatostatin in the small intestine were observed but the total amount (pmol/organ) of the peptides was unchanged. Similarly, an increase (59%) in the concentration of gastric somatostatin in exocrine atrophy was not reflected in a significant difference in the total amount. The content of enteroglucagon in the small intestine was not different in the two groups suggesting that this material was not the trophic influence leading to increased intestinal weight.

Animals↗
PubMed1985

Measurement of circulating human proinsulin concentrations using a proinsulin-specific antiserum.

Antibodies have been raised against biosynthetic human proinsulin that show less than 1% cross-reactivity with human insulin and C-peptide. A sensitive (IC50 0.16 pmol/ml; minimum detectable concentration 0.004 pmol/ml) radioimmunoassay has been developed using this antiserum and 125I-proinsulin that will measure proinsulin-like immunoreactivity in human serum without the need for prior separation of insulin or C-peptide. In healthy, fasted subjects (N = 23), the serum proinsulin concentration was 0.015 +/- 0.001 pmol/ml (mean +/- SEM). In six healthy subjects, serum proinsulin rose to 250% of basal after 120 min in response to 100 g oral carbohydrate, but to only 130% after 60 min following 25 g oral carbohydrate. The proinsulin/total immunoreactive insulin ratio and the proinsulin/C-peptide ratio fell sharply after both high and low carbohydrate loads. Endogenous human serum proinsulin-like immunoreactivity released into the circulation after 100 g carbohydrate was eluted from a Mono Q high-performance, ion-exchange column with the same retention time as biosynthetic human proinsulin. Treatment of biosynthetic proinsulin with trypsin under mild conditions led to a decrease in proinsulin-like immunoreactivity concomitant with an increase in C-peptide and insulin-like immunoreactivity, indicating that the proinsulin-specific antiserum did not preferentially recognize intermediates of proinsulin cleavage.

Adult↗
PubMed1985

Adaptation of the small intestine to induced maldigestion in rats. Experimental pancreatic atrophy and acarbose feeding.

Intestinal adaptation has been studied in rats with pancreatic atrophy induced by feeding a copper-deficient diet and penicillamine and in rats with carbohydrate maldigestion induced by feeding of an alpha-glucosidase inhibitor (acarbose). Pancreatic atrophy led to a significant increase of weight, protein, and DNA content as well as specific activities and total amounts of the enzymes sucrase and maltase in the distal but not in the proximal part of the small intestine. Plasma levels of CCK and GIP were significantly higher in rats with pancreatic atrophy, whereas plasma levels of gastrin and insulin were lower. Tissue concentrations of gastrin in the antrum and GIP in duodenum and jejunum were unchanged. Duodenal CCK and jejunal substance P, somatostatin, and VIP and ileal substance P and somatostatin were significantly decreased in rats with acinar atrophy. Glucosidase inhibition by acarbose feeding led to weight increase of the small intestine and cecum. This was more marked when acarbose was fed together with a fiber-free diet. Under these conditions the protein and DNA content also increased significantly in both gut segments and maltase and sucrase content predominantly in the distal part. Insulin plasma concentration decreased significantly in the acarbose-fed groups, whereas GIP, gastrin, and CCK plasma concentrations remained unchanged. After fiber-rich diet tissue concentrations of gastrin in the antrum and insulin in the pancreas were significantly higher and GIP concentrations in the duodenum and jejunum significantly lower than after fiber-free diet. Acarbose increased the pancreatic insulin concentration only in the fiber-free group and did not influence gastrin and GIP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗
PubMed1985

Biological and biochemical characterization of a somatostatin-producing human carcinoma established by heterotransplantation.

A somatostatin-producing human carcinoma cell line was established by heterotransplantation into athymic nude mice. The original material, which was derived from a colon tumor of a patient who had previously had bilateral ovarian tumors contained 66 ng extractable somatostatin/g tissue. Somatostatin-producing cells could be identified by immunohistochemistry within the first tumor transplants. Although initially the somatostatin concentration was low (14 ng/g) a progressive increase was observed with each successive transplantation so that after 10 passages it reached a level of 127 ng/g tissue. Analysis of tumor extracts by gel filtration and high-performance liquid chromatography indicated that somatostatin-14 was the only molecular form produced by the original and by the transplanted tumor after multiple passages. This result demonstrates that the tumor has the ability to constitutively express the prosomatostatin gene and to process the primary translation product to somatostatin-14.

Animals↗
PubMed1984

Metabolism of substance P in human plasma and in the rat circulation.

Incubation of substance P in human plasma at 37 degrees C resulted in rapid conversion to des (Arg1-Pro2) substance P (fragment 3-11) and to des (Arg1-Pro2-Lys3-Pro4) substance P (fragment 5-11). The metabolites were purified by high-performance liquid chromatography and identified by sequence analysis. These data are consistent with the hypothesis that substance P is metabolized by enzyme(s) with the specificity of dipeptidyl aminopeptidase IV (EC 3.1.14.5). Analysis by high-performance liquid chromatography of plasma extracts following intravenous infusion of Substance P (300-350 nmoles) into anaesthetized rats showed that the peptide was cleared from the circulation within 1-2 minutes. No circulating metabolites could be identified.

Animals↗
PubMed1984

Isolation and structure of guinea pig gastric and pancreatic somatostatin.

Somatostatin-14 has been isolated from guinea pig pancreas and stomach and purified to homogeneity by gel filtration, ion-exchange chromatography and reverse phase HPLC. Amino acid composition and sequence analysis indicated that guinea pig somatostatin from both tissues has the same structure as somatostatin-14 from all other mammalian species yet studied. The study has demonstrated that somatostatin-14 from gastric tissue has the same structure as the peptide from hypothalamus and pancreas.

Amino Acid Sequence↗
PubMed1984

Cyclic-AMP-dependent phosphorylation of glicentin.

Highly purified glicentin, a 69-amino-acid-residue peptide isolated from porcine intestine that contains the full sequence of glucagon and is probably biosynthetically related to glucagon, is a substrate for cyclic-AMP-dependent protein kinase in a cell-free system. Glicentin-related pancreatic peptide (residues 1-30 of glicentin) and glucagon were not phosphorylated under the same reaction conditions. It is postulated that the serine residue at position 34 of glicentin (position 2 of glucagon), that is part of the sequence Lys.Arg. His.Ser., is the probable site of phosphorylation.

Animals↗
PubMed1984

Changes in the concentration of somatostatin and substance P in the cerebrospinal fluid following injection of alcohol into the pituitary gland.

The concentration of immunoreactive somatostatin and Substance P in the cisternal cerebrospinal fluid (CSF) of patients with pain due to malignant disease has been measured before and after injection of alcohol into the pituitary fossa. Following the first injection, a rise of 108 +/- 66% in CSF somatostatin levels was observed in 7 out of 13 patients, and a rise of 87 +/- 26% in 4 out of the 5 patients undergoing a second injection. A rise of 179 +/- 99% in levels of Substance P in CSF was observed in 4 out of 8 patients after a single injection. No change in peptide concentration was detected in peripheral plasma. Changes in CSF levels did not correlate with the degree of pain relief obtained, but patients with the greatest increase in somatostatin subsequently developed diabetes insipidus. The data are consistent with our previous experience that injection of alcohol into the pituitary fossa can cause destruction to nervous tissue, in addition to the obvious destruction of pituitary gland tissue. They do not support the suggestion that hypothalamic damage is necessary in order to obtain pain relief.

Ethanol↗
PubMed1984

Fragments of prosomatostatin isolated from a human pancreatic tumour.

Six peptides from an extract of a human pancreatic tumour were purified to homogeneity by HPLC. Amino acid composition and chemical properties indicated probable structures the same as somatostatin-14, somatostatin-28 (1-12), [Met(O)8]somatostatin-28 (1-12), [Met(O)8]somatostatin-28 (1-10), somatostatin-25 (1-9) and [Met(O)5]somatostatin-25 (1-9). The structure of somatostatin-14 was confirmed by sequence analysis. The isolation of these peptides provides insight into the processing of prosomatostatin in the tumour cells.

Amino Acid Sequence↗
PubMed1983

Conversion of substance P to C-terminal fragments in human plasma.

Substance P is rapidly converted by enzyme(s) in human plasma to des-[Arg1Pro2]-substance P (fragment 3-11) and to des-[Arg1Pro2Lys3Pro4]-substance P (fragment 5-11). These metabolites were isolated by HPLC and partially sequenced. No evidence was obtained for deamidation of substance P in plasma or for the formation of the N-terminal tetrapeptide [Arg-Pro-Lys-Pro]. The data suggest that substance P is metabolized in human plasma by an enzyme with the specificity of dipeptidyl-aminopeptidase IV. Consistent with this hypothesis, the rate of degradation of substance P measured with an antibody directed against the N-terminal region is 2-3-fold greater than measured with a C-terminally directed antibody. The degrading activity of plasma was purified 522-fold and was eluted from a gel filtration column in the molecular weight zone 150 000-170 000 and from a chromatofocusing column in the pH range 4.5 to 5.5.

Amino Acid Sequence↗
PubMed1983

Circulating somatostatin concentrations in healthy and non-insulin-dependent (type II) diabetic subjects.

A technically simple radioimmunoassay for somatostatin-like immunoreactivity (SLI) in human plasma, which uses polyethylene glycol 6000 to precipitate tracer-degrading enzymes and high molecular weight interfering components, is described and validated. Fasting concentrations of SLI in peripheral plasma were similar in healthy and non-insulin-dependent diabetic (NIDD) subjects (range 3-39 pg/ml) but showed fluctuations for individuals in both groups when sampled frequently over a 60-min period. The mean coefficient of variation of SLI concentration was, however, less (8.0%; range 3-13%) in the diabetic group than in age-matched healthy subjects (19.5%; range 11-44%) (P less than 0.02). Thus the regulation of basal D cell activity or of the somatostatinergic nervous system may be altered in type II diabetic subjects. A hospital breakfast (550 kcal) was a weak stimulus for release of SLI in both healthy and diabetic subjects. The rise in plasma SLI was sustained over 120 min. An increment in plasma SLI over mean basal levels of 5.9 +/- 0.8 pg/ml was observed in young (mean age 23 yr; N = 6) control subjects, 7.9 +/- 2.0 pg/ml in older (mean age 55 yr; N = 7) control subjects and 5.9 +/- 0.6 pg/ml (mean age 62 yr; N = 7) in diabetics. Oral glucose (75 g) produced only a transient and erratic rise in plasma SLI that was not significant at any time point for either healthy or NIDD subjects. It is concluded that further investigations are necessary before hypotheses linking somatostatin deficiency with the hormonal and metabolic abnormalities of non-insulin-dependent diabetes can be accepted.

Adult↗
PubMed1982

Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats.

The gastric exocrine inhibitory activities of somatostatin-28 (SS-28) and somatostatin-14 (SS-14) were determined in conscious cats prepared with gastric fistulae. Gastric acid and pepsin secretions were stimulated with pentagastrin. Expressed in terms of exogenous doses, SS-14 (ID50: 1.49 nmol . kg-1 . h-1) was 3.4 times more potent than SS-28 (ID50: 5.12 nmol . kg-1 . h-1) as an inhibitor of gastric acid secretion. Similarly SS-14 (ID50: 0.25 nmol . kg-1 . h-1) was 3.8 times more potent than SS-28 (ID50: 0.96 nmol . kg-1 . h-1) as an inhibitor of pepsin secretion. Expressed in terms of circulating plasma concentration measured by radioimmunoassay, SS-14 (ID50: H+, 232 and pepsin 73 pM) was 8-9 times more potent than SS-28 (ID50: H+, 2112 and pepsin, 611 pM) as an inhibitor of gastric exocrine secretions. The plasma immunoreactive half-life of SS-28 (6.1 min) was double that for SS-14 (2.4 min) possibly due to a slower theoretical metabolic clearance rate of the larger peptide (30 and 87 ml . kg-1 . min-1, respectively). Both peptides had similar apparent distribution volumes (SS-14, 306 and SS-28, 263 ml . kg-1). As judged by gel chromatography of plasma samples, there was no evidence for the conversion of SS-28 to SS-14 in vivo. The reduced activity of SS-28, compared with SS-14, against gastric exocrine secretions contrasts with its more potent effects in the pituitary and pancreas.

Animals↗
PubMed1981

Metabolism of somatostatin and its analogues by the liver.

The rate of degradation of 125I-labelled [Tyr11]somatostatin by isolated rat hepatocytes was similar to that of unlabelled somatostatin. Reaction was dependent upon cell concentration and temperature, being rapid at 37 degrees C and negligible at 0 degrees C. The apparent Km for the overall degradative process was approximately the same for degradation by hepatocytes and by partially-purified liver plasma membranes. Extracellular breakdown of somatostatin, by proteases released from cells into the incubation medium, represented less than 10% of the cell-associated degradation. Homogenization of hepatocytes resulted in a 10--20-fold increase in the degrading ability of the cells. After incubation of 125I-labelled [Tyr11]somatostatin and 125I-labelled [Tyr1]somatostatin with hepatocytes, 125I-labelled tyrosine was the major radioactive product identified in the incubation medium. The rate of release of 125I-labelled tyrosine from the labelled [Tyr1]analogue was approximately 11 times greater than from the labelled [Tyr11] analogue. 125I-labelled [Tyr11]somatostatin bound to the cells in a non-saturable manner and approx. 70% of the cell-associated radioactivity could be dissociated by dilute acid. The rate of degradation of somatostatin was unchanged by reagents that inhibit the internalisation and lysosomal degradation of polypeptides by cell suspensions but was reduced by reagents that inhibit sulphydryl-dependent proteases. It is proposed that plasma-membrane associated proteolysis, involving both endo- and exopeptidases may represent the predominant degradative pathway of somatostatin in vivo.

Animals↗