scholarly journals The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro

1969 ◽  
Vol 113 (3) ◽  
pp. 473-479 ◽  
Author(s):  
R. D. G. Milner ◽  
C. N. Hales

The effect of various inhibitors on insulin release from pieces of rabbit pancreas incubated in vitro was studied. Insulin release was stimulated by glucose (3mg./ml.), leucine (5mm), tolbutamide (200μg./ml.), ouabain (10μm), a raised extracellular K+ concentration (60mm) and substitution of the Ca2+ content of the incubation medium by Ba2+ (2·5mm). (a) Mannoheptulose (6mg./ml.) inhibited glucose-stimulated insulin release only. (b) Anoxia abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide and K+, but had little or no effect on release stimulated by ouabain or Ba2+. (c) 2,4-Dinitrophenol (0·25mm) abolished or inhibited insulin release stimulated by glucose, ouabain or Ba2+. (d) Diazoxide (250μg./ml.) abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba2+ (0·25 or 1mm). Diazoxide had no effect on insulin release stimulated by Ba2+ (2·5mm) and potentiated release stimulated by K+. (e) Adrenaline (1μm) abolished insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba2+. K+-stimulated release was inhibited by adrenaline. (f) Tetrodotoxin (1μm) had no effect on insulin release stimulated by glucose, leucine, tolbutamide, ouabain, K+ or Ba2+. (g) Nupercaine (1mm) abolished insulin release stimulated by glucose or Ba2+.

1970 ◽  
Vol 47 (3) ◽  
pp. 347-356 ◽  
Author(s):  
R. D. G. MILNER

SUMMARY Pieces of rabbit pancreas were incubated in vitro in an incubation medium containing no glucose or 1·5 mg. glucose/ml. In each of these conditions the effect on insulin release of each of the essential amino acids at 5 mm concentration was studied. Leucine was the only essential amino acid that stimulated insulin release to a level which reached statistical significance in an incubation medium containing no glucose. In medium containing 1·5 mg. glucose/ml., arginine, isoleucine, leucine and lysine stimulated insulin release and phenylalanine inhibited insulin release. Glucagon, theophylline or dibutyryl cyclic adenosine monophosphate stimulated insulin release significantly in the presence of leucine but not in the presence of arginine. Arginine stimulated insulin release in the presence of leucine. The results of these experiments characterize further the difference in the mechanism of action of leucine and arginine on the pancreatic β-cell and indicate possible explanations for results obtained in other species in vivo.


1968 ◽  
Vol 108 (1) ◽  
pp. 17-24 ◽  
Author(s):  
S. L. Howell ◽  
K W Taylor

1. A method was devised for the isolation of islets of Langerhans from rabbit pancreas by collagenase digestion in order to study the influx and efflux of K+ in islets during insulin secretion. 2. Glucose-induced insulin release was accompanied by an increased rate of uptake of 42K+ by the islets of Langerhans, though this was not the case for secretion in response to tolbutamide. Ouabain significantly inhibited the uptake of 42K+ by islet tissue. 3. No significant increase in the rate of efflux of 42K+ was demonstrated during active insulin secretion. 4. Slices of rabbit pancreas were incubated in media of different K+ content, and rates of insulin release were determined. Alteration of the K+ concentration of the medium between 3 and 8mm had no effect on the rate of insulin release by pancreas slices. However, decrease of the K+ concentration to 1mm resulted in inhibition of secretion in response to both glucose and to tolbutamide. Conversely, an increase in K+ concentration increased rates of insulin release in response to both these stimuli. 5. It is concluded that, though unphysiological concentrations of K+ may influence the secretion of insulin, fluxes of K+ in the islets do not appear to be important in the initiation of insulin secretion.


1969 ◽  
Vol 44 (2) ◽  
pp. 267-272 ◽  
Author(s):  
R. D. G. MILNER

SUMMARY Pieces of pancreas from 24-day and 30-day rabbit foetuses, 1-day-old rabbits and rabbits aged approximately 8 weeks were incubated in vitro and insulin secretion into the incubation medium was measured in response to a variety of stimuli. Glucagon, leucine, ouabain and potassium were effective stimuli at all ages studied. By the criteria of response chosen for these experiments, glucose did not stimulate insulin secretion from 24-day foetal pancreas but did so when pancreas from older animals was studied. It was concluded that the foetal β cell of the rabbit on the 24th day of gestation, although morphologically immature, shows evidence of functional competence.


The Lancet ◽  
1966 ◽  
Vol 287 (7433) ◽  
pp. 351-352 ◽  
Author(s):  
D.S Turner ◽  
N Mcintyre

1974 ◽  
Vol 52 (11) ◽  
pp. 1078-1081
Author(s):  
B. Leshem ◽  
Y. Sharoni ◽  
E. Dimant

Injection of 1-deoxy-D-manno-heptulose (1-DMH, 400 mg, subcutaneously) into rats is associated with a hyperglycemia which reaches a peak after 2 h and is about half that caused by the same dose of D-manno-heptulose (MH). Insulin release from pieces of rabbit pancreas suspended in 15 mM glucose and 20 mM 1-DMH was about 20% of the release in the absence of 1-DMH. Under the same conditions MH caused a complete block of insulin release. Yeast hexokinase was inhibited to the extent of 58% and 68% by 1-DMH and MH (14.3 mM), respectively. 1-DMH is also inferior to MH as an inhibitor of crude rat liver hexokinase and glucokinase. The primary hydroxyl group on carbon-1 of MH is not required for the heptulose to exert its inhibitory effect on hexokinase.


1965 ◽  
Vol 50 (2) ◽  
pp. 301-309 ◽  
Author(s):  
Jürg Müller

ABSTRACT An extract of human urine, which was previously shown to stimulate aldosterone production by rat adrenal sections, was further purified. Evidence was obtained that its aldosterone-stimulating effect was due to the presence of ammonium ions. Addition of ammonium chloride and of urine extract to the incubation medium caused identical increases in aldosterone production in vitro. In addition to ammonium ions, rubidium and caesium ions also stimulated aldosterone production up to 250% that of control values without a significant effect on corticosterone production. Similar dose-response curves were obtained when increasing concentrations of potassium, ammonium, rubidium and caesium ions were tested. Aldosterone production was maximal at concentrations of 7 mval/1 and was significantly lower at higher concentrations. When ammonium chloride and ACTH were simultaneously added to the incubation medium, the production of aldosterone and of corticosterone was lower than with ACTH alone. On the other hand, the stimulating activity on aldosterone and corticosterone production by »TPN« (NADP) and glucose-6-phosphate was enhanced by the simultaneous addition of ammonium chloride.


1970 ◽  
Vol 64 (4) ◽  
pp. 687-695 ◽  
Author(s):  
Junzo Kato

ABSTRACT The anterior, middle, and posterior hypothalamus, the cortex cerebri, the anterior hypophysis as well as the diaphragm of adult ovariectomized rats were incubated in vitro with tritiated 17β-oestradiol. The uptake of tritiated oestradiol was differentially distributed intracerebrally with higher accumulation in the anterior hypothalamus and the hypophysis. Lowering the temperature of the incubation medium caused a reduction in the uptake of radioactivity by the anterior hypothalamus as compared to that found in other brain tissues. Tritiated oestradiol taken up in vitro by the anterior hypothalamus and the hypophysis tended to be retained after further incubation in a steroid-free medium. The addition of non-radioactive 17β-oestradiol to the medium inhibited the uptake of tritiated oestradiol by these tissues. Moreover, pretreatment with non-radioactive 17β-oestradiol in vivo prevented the preferential accumulation of tritiated oestradiol in vitro in the anterior hypothalamus and the hypophysis. These results indicate that oestradiol is preferentially taken up in vitro by the anterior hypothalamus and the hypophysis of the rat.


1960 ◽  
Vol XXXIII (III) ◽  
pp. 444-450 ◽  
Author(s):  
Maria de la Luz Suarez Soto ◽  
Jean Legault Démare

ABSTRACT Serum gonadotrophin (PMS) when added to the incubation medium of rat ovary slices increases the amount of Δ4-3-ketosteroids produced. This enhancement is proportional to the logarithm of dose. The ketosteroids were determined by their ultraviolet absorption; paper chromatography has shown that only androst-4-en-3,17-dione is present.


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