P. Schauder

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.

Impact of fish oil enriched total parenteral nutrition on DNA synthesis, cytokine release and receptor expression by lymphocytes in the postoperative period

A prospective randomized study on sixty patients was conducted to investigate the effects of a fish oil containing total parenteral nutrition (TPN) regimen in the postoperative period on lymphocyte subset distribution, proliferation, cytokine production and interleukin-2 receptor (IL-2R) expression. Patients who underwent large bowel surgery were divided into three groups. Nineteen patients received TPN with fish oil (0.2 g/kg body weight per day) plus soybean oil (1.0 g/kg per day), twenty patients received soybean oil (1.2 g/kg per day), and twenty-one patients who were on a fat-free regimen served as the control group. Natural killer (NK) cells, total, B-, T-, T4-, T8-lymphocytes, proliferation of lymphocytes, in vitro production of IL-2, IFN-gamma, TNF-alpha, and IL-2R expression were measured. Fish oil administration did not affect subset distribution and proliferation of lymphocytes. Production of interleukin-2 (IL-2), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) was augmented, and IL-2R expression less enhanced compared with the controls. It is concluded that administration of 0.2 g/kg per day fish oil after a moderate surgical stress is not immunosuppressive, but enhances the production of IFN-gamma, TNF-alpha and possibly IL-2.

Gastric inhibitory polypeptide: Effect on glucose-induced insulin release from isolated rat pancreatic islets in vitro

SummaryGastric Inhibitory Polypeptide (GIF; 1 or 10 μg/ml) potentiated glucose-induced (8 or 16.6 mM) insulin (IRI) release from isolated rat pancreatic islets. Basal release was unaffected. The threshold concentration of glucose necessary for GIF to modulate IRI release was between 6 and 8 mM. GIP had no effect on IRI release from islets submitted to a maximal glucose stimulus (25 mM).

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.

Influence of insulin on blood levels of branched chain keto and amino acids in man

Branched chain keto acids, their corresponding amino acids, glucose, glucagon, growth hormone, C-peptide and gastric inhibitory polypeptide were determined in 8 healthy subjects after an intravenous bolus injection of 0.1 U/kg insulin. Branched chain keto acids declined within 60 min, the corresponding amino acids within 20 min or later. Amino acids tended to return towards normal earlier than their keto acids. Blood glucose levels were normal 2 hr after insulin injection while keto and amino acids remained diminished for more than 3 hr. In 8 healthy controls, given physiological saline instead of insulin, the branched chain keto acids did not decline throughout the test. It is suggested that insulin diminishes blood levels of branched chain keto acids, that the intraorgan flux of branched chain keto acids is different from the flux of branched chain amino acids and that branched chain keto acids may serve to correct for hypoglycemia.

A versatile microperifusion system

Abstract A microsystem is described which enables one to correlate secretion from tissue samples with fluorometric recordings of functional parameters and with freezestop measurements of metabolite levels. Small pieces of tissue are placed on nylon gratings or membrane filters and are perifused with different media sequentially while monitoring the tissue fluorescence or collecting the perifusate containing the secretory products. By rapidly pushing a special perifusion chamber into Freon 12 kept at its melting point, the tissue is chilled to −20°C in less than 2 sec. The system has been used to study insulin release and metabolism of isolated pancreatic islets.

Cytochalasin B: Inhibition of glucose-induced insulin release from isolated rat pancreatic islets

SummaryCytochalasin B (200 μg/ml) completely inhibited the glucose-induced insulin release from isolated rat islets. Basal release was unaffected. The cytochalasin-induced inhibition was rapidly reversible. Pretreatment with cytochalasin B seemed to increase the sensitivity of islets to a subsequent glucose stimulation.

Effect of Fasting on the Release of Insulin and Somatostatin from Perifused Islets of Langerhans

Release of somatostatin and insulin from perifused islets of fasted and control rats was compared. After a fasting period of 48 h glucose-induced insulin release but not somatostatin release was diminished. Islets from fasted rats released significantly more somatostatin in the presence of 3.3 mM glucose than islets from controls. Simultaneously, the somatostatin content of isolated islets from fasting rats was significantly decreased. The results indicate that the low secretory activity of islet B cells in the fasting state is associated with a high secretory activity of islet D cells.

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

Serum branched chain amino and keto acid response to fasting in humans.

Eight healthy individuals were fasted for 72 hours. The concentrations of the branched chain keto acids (BCKA), branched chain amino acids (BCAA), C peptide, and glucagon were determined in peripheral venous blood. alpha-ketoisocaproic acid, alpha-keto-beta-methyl-n-valeric acid, and alpha-ketoisovaleric acid increased significantly within 36 hours along with the corresponding amino acids. After 60 hours of starvation, the concentrations of BCKA and BCAA declined despite the fact that the subjects were still in the fasting state. These changes were accompanied by a decrease in the concentrations of C peptide and an increase in glucagon levels. It is suggested that in starving man insulinopenia may contribute to the rise in BCKA concentrations and that the increase in BCKA may be a mechanism to reduce proteolysis.