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Biomedical subjects

B L Pimstone

Publications and source records attributed to B L Pimstone.

At least 19 recordsLinked to original sources

Peripheral plasma somatostatin-like immunoreactive responses to insulin hypoglycemia and a mixed meal in healthy subjects and in noninsulin-dependent maturity-onset diabetics.

We have measured peripheral plasma immunoreactive somatostatin (SRIF-LI) in 10 healthy subjects and 10 noninsulin-dependent maturity-onset diabetics (NIDDM). The mean (+/-SE) basal level of SRIF-LI in NIDDMs of 185 +/- 27 was similar to that of 174 +/- 23.5 pg/ml in age-, weight-, and sex-matched healthy subjects. Insulin hypoglycemia of equivalent magnitude induced a 113 +/- 15.8 pg/ml increase in SRIF-LI 40 min after injection in healthy subjects and no significant change in the NIDDMs. Ingestion of a mixed meal induced a biphasic rise with a mean peak of 75 +/- 30 pg/ml above basal at 15 min and a later peak of 130 +/- 35 pg/ml above basal at 120 min in healthy subjects. In NIDDM, there was no significant rise above basal, and the differences were significant at 15 and 120 min. Our findings are compatible with deficient SRIF release in these NIDDM in whom the deficient SRIF secretion may contribute to the hyperglycemia.

Adult

Substance P release from rat hypothalamus and spinal cord.

A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 microM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested.

Animals

Tissue and serum somatostatin-like immunoreactivity in lean and obese Zucker rats.

Tissue and serum somatostatin levels were measured in genetically lean and obese Zucker rats. Immunoreactive somatostatin content was decreased in three central nervous system regions (hypothalamus, septum and preoptic area and thalamus) of obese rats but was increased in cerebral cortex. No differences were observed in antral or colonic somatostatin content but obese animals had significantly elevated pancreatic levels. Portal vein somatostatin-like immunoreactivity in contrast was significantly lower in obese rats. The widespread alterations in tissue and serum somatostatin-like immunoreactivity suggest either a diffuse abnormality of somatostatin physiology or a response to a generalised feature of the obese hyperinsulinaemic state.

Animals

Ultracentrifugation evidence for a somatostatin-binding protein in serum.

Using a technique of high speed centrifugation of serum and a well validated immunoassay for the measurement of serum somatostatin-like immunoreactivity, we have demonstrated that somatostatin, unlike other peptide hormones, appears to sediment with large molecular weight proteins. When synthetic somatostatin of increasing concentration was incubated with serum prior to ultracentrifugation, a linear plot of concentration of somatostatin added against concentration sedimenting (or apparently bound to protein) revealed an association curve. These data provide further evidence for the existence of a serum-binding protein for somatostatin.

Adult

Tissue and serum somatostatin-like immunoreactivity in fed, 15-h-fasted, and 72-h-fasted rats.

Somatostatin-like immunoreactivity (SLI) was measured in extracts of gastric antrum, colon, pancreas, and central nervous system, as well as in unextracted portal and inferior vena caval serum from fed, 15-h-fasted, and 72-h-fasted rats. No differences were found in SLI in the central nervous system of the three groups. However, striking variations were found in the gastrointestinal tract and pancreas; the antrum, colon, and pancreas of 15-h-fasted rats contained the least SLI, the content being significantly elevated in these three areas after feeding and after a 72-h fast. Portal serum levels were highest after feeding but lowest in 72-h-fasted rats, in spite of high intestinal and pancreatic SLI content in both. These tissue and serum differences suggest a physiologic role for SLI in nutrient homeostasis not only at tissue level, but also putatively as a hormone in the portal system.

Animals

Somatostatin--paracrine and neuromodulator peptide in gut and nervous system.

Somatostatin, a tetradecapeptide widely distributed in nervous tissue and gut, has inhibitory effects on secretion and neuromuscular activity. The actions of this peptide probably embrace three types of transmitter-receptor interaction, namely that of a neurotransmitter in the nervous system, that of a hormone in the hypophyseal portal circulation and that of a local (paracrine) effector in gut and pancreas.

Animals

Sulphation factor (somatomedin activity) in experimental protein malnutrition in the rat.

In a rat model of protein malnutrition in which the failure of growth is a major feature, a low level of bioassayable sulphation factor activity was present in the serum, associated with normal levels of growth hormone and low insulin in the plasma. The administration of pharmacological doses of human or bovine growth hormone did not increase the amount of sulphation factor activity in the serum or the width of the tibial epiphyses in the protein-malnourished animals. The basal and serum-stimulated incorporation of 35SO2-4 into the costal cartilages of malnourished animals did not differ from that of controls, which suggests that the responsiveness of the end-organs was normal.

Animals

Generation of somatomedin activity in response to growth hormone and insulin from isolated perfused livers of normal and protein-malnourished rats.

The generation of somatomedin activity by isolated perfused livers was examined in protein-malnourished (4% casein diet) and well-nourished (controls, 20% casein diet) rats. There was significantly less somatomedin activity (measured by the porcine costal cartilage bioassay), after perfusion for 2 h, in the perfusates from the livers of malnourished rats both in hormone-free perfusates and perfusates containing hormones (10 microgram GH/ml, 1000 microunits insulin/ml or a combination of the two). A reduction in the somatomedin activity generated by the liver may be the mechanism responsible for the low serum level of somatomedin (in spite of raised or normal levels of growth hormone) in human or experimental protein malnutrition.

Animals

The characterization of somatostatin-like immunoreactivity in human serum.

We describe the characterization of somatostatin-like immunoreactivity (SRIF-LI) found by radioimmunoassay (RIA) to be present in normal human serum. Degradation by serum of 125I-Tyr1 SRIF in the assay, as assessed by chromatoelectrophoresis and immunoprecipitation, was overcome by using EDTA in the assay buffer and Trasylol in the blood samples. Serum samples thus obtained from 48 normal subjects revealed a bimodal distribution of SRIF-LI; 92 per cent (group 1) had a mean level of 0.274 +/- 0.009 ng. per milliliter. What was measured in these sera showed identity to synthetic SRIF on serial dilutions, Sephadex G-25 chromatography, and thin-layer chromatography, and it was shown to be immunoreactive by an antibody-Sepharose affinity system. Higher levels (1.0 +/- 0.041 ng. per milliliter) were found in 8 per cent of the sera; 50 per cent of this material behaved identically as serum SRIF-LI from group 1. The remainder proved to be heterogeneous, consisting of two peaks of large molecular weight, both of which shared immunologic identity with synthetic SRIF as shown by binding to the antibody-Sepharose affinity system. Their further nature is unknown.

Adult