Christopher McIntosh

Somatostatin and insulin release from isolated rat pancreatic islets stimulated by glucose

Somatostatin inhibits insulin release in vivo [l-5 J and in vitro [6-lo] after exogenous administration. This inhibitory action was discovered at a time when only the hypothalamus and some extrahypothalamic areas in the central nervous system were known to contain somatostatin-producing cells [ 1 l-l 21. The suggestion that somatostatin might be of physiological importance in the regulation of insulin secretion was, therefore, based on the assumption that somatostatin is released into the peripheral circulation and transported to the B-cell membrane at concentrations high enough to block secretion of insulin. The discovery that the D-cells of the islets of Langerhans react with antisomatostatin serum suggested local effects of the polypeptide via paracrine secretion. Somatostatin may indeed play a physiological role in the release of insulin [ 13171. We now present evidence that somatostatin is released from isolated rat pancreatic islets and that insulin and somatostatin release are interrelated.

Fluoride determination in plasma by ion selective electrodes: A simplified method for the clinical laboratory

A potentiometric method for the determination of fluoride (F-) in serum and plasma is proposed; it is based on a combination of the single-known-addition method and the electrode slope-by-dilution method. This procedure provides reliable results in extremely low measuring ranges down to 2.5 mug/l, where the electrode slope deviates markedly from Nernstian behaviour. In this method no electrode calibration is required and only one standard is necessary. 1 ml of plasma is sufficient for one analysis. Apart from a 5% enrichment of all samples with a concentrated total ionic strength adjustment buffer, no further preparation of the sample is required. The simplicity of the various pipetting and analytical steps, and also of the evaluation of the readings, may render this method highly suitable for the clinical laboratory. Investigations into the accuracy and precision of the method produced satisfactory results. The recovery in plasma amounted to 99.7%, even in the low measuring ranges. The discrimination capacity of the method amounts to 0.1 mug/l. With the apparatus and experimental procedures described, 18 plasma analyses per day can be performed even at low F- concentrations with which longer electrode stabilization periods are required. Storage of the plasma samples frozen at --20 degrees C for up to 8 weeks exerts no effect on the F- concentration. Problems of sample contamination and other disturbances are discussed. Determinations of normal values in 20 test subjects resulted in a mean value of 10.4 plus or minus 4.01 mug/l (Mean plus or minus S.D.). The modal value amounted to 9.5 mug/l, and the range was between 5.9 and 18.8 mug/l. The F- content of the drinking water supplied to this group of persons amounted to 180 mug/l. The importance of the method has been illustrated using a clinico-nephrological study as an example.

Somatostatin and insulin release from isolated rat pancreatic islets in response to D-glucose, L-leucine, α-ketoisocaproic acid or D-glyceraldehyde: Evidence for a regulatory role of adenosine-3′,5′-cyclic monophosphate

Abstract Somatostatin and insulin release from isolated rat pancreatic islets was stimulated by glucose, leucine or α-ketoisocaproic acid. D-glyceraldehyde stimulated insulin release but diminished the secretion of somatostatin. Glucagon and theophylline amplified the glucose-induced somatostatin release. A regulatory role of the D-cells adenylate cyclase/phosphodiesterase system for the release of somatostatin is suggested. Furthermore, stimulation as well as inhibition of somatostatin release might be of significance for the secretory function of the B-cell.

Comparative calcium ion determinations in plasma and whole blood with a new calcium ion analyzer

A new Ca2+ analyzer has been used for the determination of Ca2+ in plasma and whole blood from normal subjects and patients with disorders of calcium metabolism. The results were nearly identical: the equation of the regression line was y=1.02x-0.037 and the coefficient of correlation r=0.998. The possibility of using whole blood for measurement with concomitant simplification of the anaerobic sample preparation is an obvious advantage.

Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months

Abstract. In twenty‐two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values >4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5–10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non‐responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.

Dynamics of somatostatin release from isolated rat pancreatic islets.

1. Introduction Isolated islets of Langerhans release somatostatin in response to glucose [l] , CAMP [2] , Lu-ketoisocaproic acid, glucagon and theophylline [3]. The aim of the present study was to investigate the interactions that might exist between the secretion of somatostatin and insulin, i.e., a possible D-cell/B-cell interrelationship. A static incubation system, as previously used [l-3], is of limited help for this purpose because it does not give information on the dynamics of the respective release processes. Therefore, the kinetics of somatostatin and insulin release from isolated rat islets were investigated in a perifusion system. 2. Materials and methods Fed, male Wistar rats (220-270 g) were used throughout the study. Bovine serum albumin was purchased from Behringwerke A. G., Marburg, FRG; 12SI-labeled porcine insulin (spec. act. 1 SO-200 mCi/ mg) from Farbwerke Hoechst A. G., Frankfurt, FRG; crystalline rat insulin from Serono, Freiburg, FRG; collagenase from Worthington Biochemical Co., USA. Islets were isolated from rat pancreas by collagenase 2 h after intraperitoneal administration of 0.6 ml pilocarpine hydrochloride (2% w/v), as previously described [4,5] and perifused for 90 min with Krebs- Ringer bicarbonate buffer (0.2 mg/ml BSA; 1000 KIU/ml Trasylol @), 2 mM or 25 mM glucose with or without 5 mM theophylline, pH 7.4,37”C), 0.9 ml/min flow rate, 300 islets/perifusion [6] . All perifusions were preceded by a preperifusion period of 30 min with 2 mM glucose. Insulin release into the medium was determined

Gastrointestinal somatostatin in man and dog

Abstract The concept of a role for somatostatin in gastrointestinal physiology has developed from several observations. Infusion of somatostatin is capable of suppressing pancreatic and gastrointestinal hormone release, 1,2 gastric secretion, 3 pancreatic juice and enzyme secretion, 4 and gallbladder contraction. 4 Immunohistology has revealed a widespread distribution of somatostatin-containing cells in pancreas, stomach, duodenum, and jejunum 5,6 and the D cell appears to be the specific locus in pancreas and gastric antrum. 5,6 Radioimmunoassay has confirmed the gastrointestinal localization in rat 7–10 and chicken. 11 The demonstration of secretion of somatostatin from isolated rat pancreatic islets incubated in vitro 11–13 implies a regulatory role for this polypeptide. The present report examines the distribution of immunoreactive somatostatin in the gastrointestinal system of dog and man and the question of multiple molecular forms in these organs.

Labelled antibody membrane assay for parathyroid hormone a new approach to the measurement of receptor bound hormone.

Abstract A new method is described for the measurement of hormone bound to membrane receptors. Antibodies specific for the C-terminal and N-terminal regions of parathyroid hormone were labelled with 125 I and incubated with renal membranes which had been previously incubated with unlabelled hormone. The uptake of hormone demonstrated pH and time dependence and was a saturable process. Treatment of the membranes with acid or heating to 100°C, or inactivation of the hormone with hydrogen peroxide, completely abolished detectable hormone uptake to the membranes.

Somatostatin and Gastrin Release from Canine Stomach

Somatostatin and gastrin release into the veins draining the stomach was studied in 27 anaesthetized dogs. Basal somatostatin-like immunoreactivity (SLI) in corpus veins (136 +/- 36 pg/ml) was significantly higher than in antrum veins (83 +/- 20 pg/ml; p less than 0.05) and the femoral artery (58 +/- 15 pg/ml; p less than 0.02). During peptone, pH 6.5, perfusion of the stomach, SLI concentration increased significantly in the corpus veins to approximately four times basal and in the antrum veins to three times basal, whereas SLI levels in the peripheral circulation remained constant. Peptone, pH 3.5, and sodium oleate did not stimulate gastric SLI. Gastric distension increased significantly SLI release from the corpus. In gel filtration studies 50%--70% of SLI from gastric vein plasma samples but greater than 90% from femoral artery samples eluted in the void volume of Sephadex G-25 columns. Gastrin secretion was stimulated significantly only by peptone, pH 6.5.

Dynamics of somatostatin and insulin release from isolated rat pancreatic islets: Evidence for intraislet interactions between B cells and D cells☆

Abstract Glucose stimulates the release of somatostatin and insulin from isolated rat pancreatic islets. 1 This stimulation appears to be mediated via the islets adenylate cyclase-phosphodiesterase system. 2 However, the dynamics of both secretory processes are different. In particular, islets previously exposed to a medium containing a high glucose concentration respond with an immediate decrease in insulin release and a transient increase in somatostatin release when the glucose concentration is suddenly lowered. 3 This suggests that somatostatin release is stimulated by glucose but might be inhibited by phenomena associated with a high secretory activity of B cells. The aim of the present study is to further characterize the apparent intraislet interactions between B cells and D cells.