scholarly journals The role of adenosine 3′:5′-cyclic monophosphate in the regulation of insulin release by isolated rat islets of Langerhans

1971 ◽  
Vol 122 (1) ◽  
pp. 115-120 ◽  
Author(s):  
W. Montague ◽  
J. R. Cook
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Islet Cells ◽  
Intracellular Concentration ◽  
Release Process ◽  
Cyclic Monophosphate ◽  
Extracellular Glucose ◽  
Rat Islets Of Langerhans ◽  
Effect Of Glucose

1. Concentrations of cyclic AMP (adenosine 3′:5′-cyclic monophosphate) and rates of insulin release were measured in islets of Langerhans isolated from rat pancreas and incubated for various times in the presence of glucose, 3-isobutyl-1-methylxanthine, caffeine, theophylline, adrenaline and diazoxide. 2. Caffeine and theophylline produced small but significant increases in both cyclic AMP and release of insulin when they were incubated in the presence of 10mm-glucose. 3. 3-Isobutyl-1-methylxanthine produced a marked increase in the intracellular concentration of cyclic AMP in the presence of 5mm- and 10mm-glucose. However, insulin release was stimulated only in the presence of 10mm-glucose. 4. In response to rising concentrations of extracellular glucose (5–20mm) there was no detectable increase in the intracellular concentration of cyclic AMP even though there was a marked increase in the rate of insulin release. 5. In response to 10mm-glucose insulin release occurred in two phases and 3-isobutyl-1-methylxanthine potentiated the effect of glucose on both phases. The intracellular concentration of cyclic AMP remained constant with glucose and rose within 10min to its maximum value with 3-isobutyl-1-methylxanthine. 6. Adrenaline and diazoxide inhibited insulin release and lowered the intracellular concentration of cyclic AMP when islets were incubated with glucose or 3-isobutyl-1-methylxanthine. 7. It is suggested that glucose does not stimulate insulin release by increasing the concentration of cyclic AMP in islet cells. However, the concentration of cyclic AMP in islet cells may modulate the effect of glucose on the release process.

scholarly journals The role of adenosine 3′:5′-cyclic monophosphate in the regulation of insulin release. Properties of islet-cell adenosine 3′:5′-cyclic monophosphate phosphodiesterase

1972 ◽  
Vol 129 (4) ◽  
pp. 945-952 ◽  
Author(s):  
D. J. Sams ◽  
W. Montague
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Gel Filtration ◽  
Apparent Molecular Weight ◽  
Supernatant Fraction ◽  
Phosphodiesterase Activity ◽  
Ph Optimum ◽  
Cyclic Monophosphate ◽  
Km Value

1. An assay has been developed with sufficient sensitivity for determination of the adenosine 3′:5′-cyclic monophosphate diesterase activity in islets of Langerhans, and has been used to investigate the response of the enzyme to various agents which are known to affect insulin release. 2. The subcellular distribution of the enzyme in islets of Langerhans prepared from guinea-pig pancreas was investigated and over 70% of the activity present in the original homogenate was recovered in the supernatant fraction. 3. Gel filtration of the activity present in the supernatant fraction on Sephadex G-200 gave a single peak of activity with an apparent molecular weight of 200000. The phosphodiesterase activity in the peak fraction showed two apparent Km values for adenosine 3′:5′-cyclic monophosphate (cyclic AMP) of 3μm and 30μm, suggesting the presence of two activities. The pH optimum of the activity with the low Km value was 8.7. 4. Theophylline, caffeine, 3-isobutyl-1-methylxanthine (SC-2964), glibenclamide, tolbutamide, xylitol and leucine were inhibitors of the activity with the low Km value; imidazole and arginine stimulated the activity, and glucose and diazoxide were without significant effect. 5. It is suggested that the agents theophylline, caffeine, SC-2964, glibenclamide, tolbutamide, leucine and imidazole may alter the intracellular concentration of cyclic AMP in islets of Langerhans by affecting the cyclic AMP phosphodiesterase activity in islet cells and in this way may affect insulin release.

scholarly journals Effects of monensin on metabolism of isolated rat islets of Langerhans

1984 ◽  
Vol 223 (2) ◽  
pp. 423-432 ◽  
Author(s):  
J E Smith ◽  
S L Howell
Keyword(s):  
Insulin Release ◽  
Islets Of Langerhans ◽  
Islet Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Islets ◽  
Islet Volume ◽  
Isolated Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Isolated Rat

Monensin, a univalent ionophore, is a carboxylic acid produced by Streptomyces cinnamonensis. It will complex various alkali-metal ions, but most readily binds Na+. Because of interest in the possible role of Na+ in the regulation of insulin secretion, we examined its effects on several aspects of the metabolism of isolated rat islets of Langerhans. The ionophore inhibited glucose-stimulated insulin release in a concentration-dependent manner, completely inhibiting secretion evoked by 20 mM-glucose at concentrations as low as 0.1 microM in static incubations. In perifusion experiments, both phases of insulin release were equally affected. Monensin (0.1 microM) had no significant effect on glucose oxidation as measured by the generation of 14CO2 from [14C]glucose. Monensin increased the rate of 22Na+ efflux from preloaded islets and net 22Na+ uptake over 30 min, in the absence of changes in islet volume or extracellular space. The ionophore increased the Rb+/K+ permeability of islet cells, as shown by its inhibition of 86Rb+ retention and stimulation of 86Rb+ efflux. At 0.1 microM, monensin abolished glucose-stimulated 45Ca2+ uptake by islets during 5 min incubations, and stimulated 45Ca2+ efflux from preloaded islets perifused with Ca2+-free medium, even in the complete absence of extracellular Na+. Studies of the uptake of 14C-labelled 5,5-dimethyloxazolidine-2,4-dione showed that 0.1 microM-monensin increased net intracellular pH from 7.05 to 7.13. 7 Monensin has widespread, complex, effects on the secretory responses and ion handling by the B cells, which are difficult to interpret in terms solely of actions as a Na+ ionophore.

scholarly journals Stimulation of Adenylate Cyclase by Ca2+ and Calmodulin in Rat Islets of Langerhans: Explanation for the Glucose-induced Increase in Cyclic AMP Levels

Diabetes ◽  
1980 ◽  
Vol 29 (1) ◽  
pp. 74-77 ◽  
Author(s):  
G. W. G. Sharp ◽  
D. E. Wiedenkeller ◽  
D. Kaelin ◽  
E. G. Siegel ◽  
C. B. Wollheim
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Islets Of Langerhans ◽  
Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Stimulation Of

Calcium distribution in islets of Langerhans: a study of calcium concentrations and of calcium accumulation in B cell organelles

1975 ◽  
Vol 19 (2) ◽  
pp. 395-409
Author(s):  
S.L. Howell ◽  
W. Montague ◽  
M. Tyhurst
Keyword(s):  
Endoplasmic Reticulum ◽  
Cyclic Amp ◽  
B Cell ◽  
Islets Of Langerhans ◽  
Cyclic Gmp ◽  
Cell Organelles ◽  
Calcium Accumulation ◽  
Labile Pool ◽  
Storage Granules ◽  
Rat Islets Of Langerhans

Calcium concentrations of various pancreatic B cell organelles have been determined by X-ray microanalysis of areas of frozen sections of unfixed rat islets of Langerhans. Highest concentrations were detected in storage granules and in mitochondria, although calcium was also present in nuclei, in areas of endoplasmic reticulum and of cytoplasm. Accumulation of 45Ca by isolated organelles has been studied in homogenates and isolated subcellular fractions of rat islets of Langerhans. In the presence of a permeant anion (oxalate or phosphate), accumulation of 45Ca into mitochondria and microsomes was strongly stimulated by ATP. This net uptake was diminished during incubation of homogenates or of a mitochondria plus storage granule-rich fraction in the presence of cyclic AMP, dibutyryl cyclic GMP; 2:4-dinitrophenol or of ruthenium red. Investigations of the characteristics of 45Ca accumulation by homogenates prepared from storage granule-depleted islets showed no differences from those of normal islets, suggesting that the granules do not represent an important labile pool of calcium. With the exception of cyclic AMP and cyclic GMP none of the insulin secretagogues tested (glucose, leucine, arginine, adrenalin, noradrenalin, theophylline, glibenclamide) altered calcium accumulation by islet homogenates. On the basis of absolute calcium levels and of 45Ca uptake studies it is concluded that islet B cells contain a readily exchangeable mitochondrial calcium pool, and an endoplasmic reticulum pool containing a lower concentration of calcium which is also readily exchangeable. The storage granules, despite their high calcium content, do not appear to constitute a labile pool. It seems likely that the labile mitochondria and endoplasmic reticulum pools play a predominant role in the regulation of cytoplasmic free calcium levels, which may in turn be important in the regulation of rates of insulin secretion.

scholarly journals Cytotoxic effects of streptozotocin and N-nitrosomethylurea on the pancreatic B cells with special regard to the role of nicotinamide–adenine dinucleotide

1974 ◽  
Vol 140 (3) ◽  
pp. 487-494 ◽  
Author(s):  
Rolf Gunnarsson ◽  
Christian Berne ◽  
Claes Hellerström
Keyword(s):  
Insulin Release ◽  
Islet Cells ◽  
Cytotoxic Action ◽  
Glucose Residue ◽  
Cytotoxic Effects ◽  
Pancreatic B Cells ◽  
Effect Of Glucose ◽  
Oxidation Of Glucose ◽  
Nad Depletion

The effects on the pancreatic B cell of streptozotocin and its aglucone derivative N-nitrosomethylurea were investigated in obese–hyperglycaemic mice and their lean littermates. Both streptozotocin and N-nitrosomethylurea were found to be B-cytotoxic although N-nitrosomethylurea produced less islet damage. Both substances decreased the concentrations of NAD+ in the islet cells to about 10% of the control values within 2h after injection. This NAD+ depletion was prevented by injection of nicotinamide 10min after the administration of streptozotocin or N-nitrosomethylurea. In islets taken from animals 10min after injection of streptozotocin or N-nitrosomethylurea there was no stimulatory effect of glucose on the respiration or insulin release and the oxidation of glucose was markedly decreased. Addition of nicotinamide (10mm) to the incubated islets restored glucose stimulation of both the oxygen consumption and insulin release. It is concluded that islet NAD+ depletion is probably important for the B-cytotoxin action of N-nitrosomethylurea and streptozotocin. The glucose residue in the streptozotocin molecule may potentiate the B-cytotoxic action of this drug in mice.

Nicotinamide Prevents Interleukin-1 Effects on Accumulated Insulin Release and Nitric Oxide Production in Rat Islets of Langerhans

Diabetes ◽  
1994 ◽  
Vol 43 (6) ◽  
pp. 770-777 ◽  
Author(s):  
H. U. Andersen ◽  
K. H. Jorgensen ◽  
J. Egeberg ◽  
T. Mandrup-Poulsen ◽  
J. Nerup
Keyword(s):  
Nitric Oxide ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Interleukin 1 ◽  
Nitric Oxide Production ◽  
Rat Islets ◽  
Oxide Production ◽  
Rat Islets Of Langerhans
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