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M Berelowitz

Publications and source records attributed to M Berelowitz.

99 records · Page 6Linked to original sources

Somatostatin-like immunoreactivity in rat blood. Characterization, regional differences, and responses to oral and intravenous glucose.

Somatostatin-like immunoreactivity (SLI) has been demonstrated by radioimmunoassay (RIA) in rat serum using an antiserum specific for somatostatin and cross-reacting maximally with the biologically important area on the peptide. The RIA has a sensitivity of 35 pg/ml. SLI dilutes in parallel with synthetic somatostatin standard in the RIA and shows characteristics similar to synthetic somatostatin on Sephadex G-25 (f) gel chromatography eluting largely as a single peak with 1 M acetic acid. Significant regional differences in serum SLI are present. A positive gradient was found in paired samples from aorta (mean+/-SEM, 0.304+/-0.024 ng/ml) and portal vein (0.495+/-0.047 ng/ml) consistent with the known presence of somatostatin in gut and pancreas, and a negative gradient was noted between paired samples from portal vein (0.523+/-0.076 ng/ml) and hepatic vein (0.290+/-0.048 ng/ml) indicating hepatic clearance. No significant differences were demonstrated between aorta and confluence of cerebral venous sinuses or between aorta and inferior vena cava (IVC). After intragastric glucose, a significant and marked elevation of portal SLI was observed, maximal at 5 min (0.416+/-0.137 vs. 1.55+/-0.30 ng/ml at 5 min). A significant biphasic elevation of portal SLI also occurred after intravenous glucose. After both routes of glucose administration, the patterns of portal SLI followed closely those of portal glucose and insulin. By contrast, IVC SLI failed to reflect these changes.Thus, SLI in the rat shows chromatographic similarity with synthetic somatostatin. Regional differences in serum levels are marked; the highest concentrations being found in the portal venous effluent of pancreas and gut. Furthermore, glucose causes elevation of portal SLI in a pattern similar to portal insulin and glucose and without concomitant elevation in IVC. This differential elevation of SLI after glucose is consistent with a hormonal action within the portal system as a direct effect of somatostatin on the liver has previously been demonstrated. In addition, the liver is important in the clearance of portal SLI, possibly to prevent extraportal effects in response to gut and pancreatic stimulation. Finally, it is clear that regional sampling of serum for SLI measurement may be critical in the investigation of the putative physiological roles for somatostatin.

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↗

The characterization of growth hormone release inhibiting hormone-like immunoreactivity in normal urine.

Using a previously described radioimmunoassay for growth hormone release inhibiting hormone (GH-RIH), the presence of GH-RIH-like immunoreactivity in urine has been characterized by demonstrating mobility identical to synthetic GH-RIH standard on two sephadex gel chromatographic systems, and parallelism of dilutions of the sephadex fractions with synthetic GH-RIH. Furthermore, 74% of the sephadex fraction cross-reacting in the immunoassay bound to antibody conjugated to sepharose and could be eluted by 1 M acetic acid. This immunospecific eluate showed identity with synthetic GH-RIH on both ion exchange and thin layer chromatography. Thus GH-RIH-like immunoreactivity is present in normal urine; this may have potential relevance in the search for a physiological role for this peptide.

Humans↗

Somatostatin, 1976.

Somatostatin, a growth hormone release-inhibiting factor, isolated originally from the hypothalamus, has been shown to have widespread effects on brain and endocrine and exocrine pancreatic and gut function. Furthermore, it has a widespread distribution in the CNS, gut and C cells of the thyroid -- cells which probably migrated originally from the neural crest during development. While the pharmacological effects of somatostatin are diffuse, its physiological role is at present unknown, but in view of its concentration in synaptosomal fractions of neural tissue, it may have a neurotransmitter or a synaptic modulator function.

Animals↗

A radioimmunoassay for growth hormone release-inhibiting hormone: method and quantitative tissue distribution.

A specific antiserum has been produced to haemocyanin conjugaed synthetic growth hormone release inhibiting hormone (GHRIH). This has allowed the development of a radioimmunoassay for GHRIH sensitive to 5 pg/tube. GHRIH content in 2 m acetic acid extracts of rat tissues have been measured and show the majority to be CNS-especially hypothalamus and septum and preoptic areas with substantial amounts in spinal cord and thalamus. Extra neurological localization in pancreas, gastric antrum, colon and thyroid have been demonstrated.

Animals↗

Differential effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion.

The effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion were compared in normal men to search for possible hypothalamic or pituitary inhibitory effects of proinsulin on glucocounterregulatory responses. When subjects received 0.1 U/kg i.v. human insulin and 25-38 micrograms/kg i.v. human proinsulin on separate occasions, plasma glucose decreased more rapidly after insulin, and the nadir was slightly lower, but integrated hypoglycemic responses were similar. Cortisol, growth hormone (GH), prolactin, epinephrine, and norepinephrine responses occurred more rapidly after insulin than after proinsulin. Peak and integrated cortisol, GH, and catecholamine responses to insulin and proinsulin were similar, but those of prolactin were reduced after proinsulin when compared with insulin by 42% (P less than .01) and 34% (P less than .05), respectively. When euglycemia was maintained by a variable glucose infusion rate after the injection of insulin and proinsulin, no differences were observed in plasma levels of any of the hormones. The intravenous injection of a dose of proinsulin (6 micrograms/kg), which did not produce hypoglycemia but was the molar equivalent of insulin used in the first protocol, failed to modify the GH or prolactin responses to a combined injection of GH-releasing hormone (1 microgram/kg) and thyrotropin-releasing hormone (500 micrograms). Our results indicate that the onset of pituitary hormone and catecholamine responses to hypoglycemia are related to the rate of plasma glucose decline, with the slower responses to proinsulin reflecting a more gradual onset of hypoglycemia. The magnitude of the cortisol, GH, and catecholamine responses, however, was comparable with proinsulin- and insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of the counterregulatory hormone response to semisynthetic human insulin and purified porcine insulin in normal subjects and patients with type I diabetes mellitus.

The counterregulatory hormone responses to semisynthetic human insulin and purified porcine insulin were compared in 20 healthy volunteers (ten men and ten women) and 16 patients (8 men and 8 women) with type I diabetes mellitus (IDDM). In both groups blood glucose fell to similar levels following insulin administration; no difference in counterregulatory hormone response or hypoglycemic awareness was noted when comparing human to porcine insulin. However, when men were compared to women, significant differences were noted in basal glucagon, cortisol, and growth hormone levels, as well as in norepinephrine, prolactin, and cortisol responses to hypoglycemia. These differences could not be attributed to insulin species, different doses of insulin, or degree of hypoglycemia. These findings suggest that hormonal response to and awareness of hypoglycemia are similar in healthy subjects and patients with IDDM following administration of human and porcine insulin and that hormonal responses in men and women should be studied separately to avoid confusion in interpreting results arising from differences in sex.

Adult↗