Direct long-term effect of hydrocortisone on insulin and glucagon release from mouse pancreatic islets in tissue culture

1981 ◽  
Vol 96 (4) ◽  
pp. 498-504 ◽  
Author(s):  
J. Brunstedt ◽  
J. Høiriis Nielsen
Keyword(s):  
Tissue Culture ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Endocrine Function ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Long Term Effect ◽  
Mouse Pancreatic Islets ◽  
Pancreatic Endocrine Function ◽  
Mouse Islets

Abstract. The effects of glucocorticoids on the pancreatic endocrine function was studied in isolated mouse pancreatic islets maintained in tissue culture for 1 to 3 weeks. Following culture for 1 week without corticoid supplement acute experiments with hydrocortisone showed no significant effect on the glucose-induced insulin release at 10−8 to 10−5 mol/l hydrocortisone. When, however, the islets were cultured in the presence of hvdrocortisone, there was an increased insulin release to the medium in a dose-dependent manner, with the maximal effect at 10−7 mol/l hydrocortisone. The release of glucagon to the medium was not affected to the same degree, but showed a slight inhibition at increasing concentrations of hydrocortisone. Short-term experiments after the culture period showed that islets cultured for 3 weeks in the presence of 10−7 to 10−5 mol/l hydrocortisone had an enhanced insulin secretion in response to glucose. The islets did not show any statistically significant change in their insulin- and DNA-content after 3 weeks of culture with hydrocortisone, but a marked reduction in the content of glucagon was found with increasing concentrations of hydrocortisone. The present results suggest that physiological concentrations of hydrocortisone are of importance for mouse islets to maintain their insulin production in tissue culture.

scholarly journals Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture

1974 ◽  
Vol 140 (3) ◽  
pp. 377-382 ◽  
Author(s):  
Arne Andersson
Keyword(s):  
Tissue Culture ◽  
B Cells ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Mouse Pancreatic Islets

Rates of glucose oxidation and insulin release in response to a wide range of glucose concentrations were studied in short-term experiments in isolated mouse pancreatic islets maintained in tissue culture for 6 days at either a physiological glucose concentration (6.7mm) or at a high glucose concentration (28mm). The curves relating glucose oxidation or insulin release to the extracellular glucose concentration obtained with islets cultured in 6.7mm-glucose displayed a sigmoid shape similar to that observed for freshly isolated non-cultured islets. By contrast islets that had been cultured in 28mm-glucose showed a linear relationship between the rate of glucose oxidation and the extracellular glucose concentration up to about 8mm-glucose. The maximal oxidative rate was twice that of the non-cultured islets and the glucose concentration associated with the half-maximal rate considerably decreased. In islets cultured at 28mm-glucose there was only a small increase in the insulin release in response to glucose, probably due to a depletion of stored insulin in those B cells that had been cultured in a high-glucose medium. It is concluded that exposure of B cells for 6 days to a glucose concentration comparable with that found in diabetic individuals causes adaptive metabolic alterations rather than degeneration of these cells.

Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets

1986 ◽  
Vol 250 (2) ◽  
pp. E107-E113 ◽  
Author(s):  
H. Kofod ◽  
B. Hansen ◽  
A. Lernmark ◽  
C. J. Hedeskov
Keyword(s):  
Glutamate Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Insulin Release ◽  
Maximal Effect ◽  
Terminal Sequence ◽  
Terminal Part ◽  
Mouse Pancreatic Islets ◽  
Glutamate Dehydrogenase Activity ◽  
Mouse Islets

Peptides representing the C-terminal end of secretin were synthetized and their effects tested along with secretin on column-perifused isolated mouse pancreatic islets. Insulin release induced by 10 mmol/l D-glucose was potentiated by secretin tested in a concentration range of 0.01-10 micrograms/ml; the maximal effect was obtained with 1 microgram/ml secretin. This effect was mimicked by 50-500 micrograms/ml NH2-Leu-Leu-Gln-Gly-Leu-Val-NH2, [S-(22-27)], which represents an amidated C-terminal sequence of the secretin molecule. The consecutive smaller secretin C-terminal peptides had either no effects [Val-NH2, S-(24-27)] or only marginally [S-(26-27), S-(23-27)] potentiating effects on insulin release in the presence of 10 mmol/l D-glucose. The effects of secretin and S-(22-27) were not influenced by 2 mmol/l glutamine. The intact hormone and the five synthetic peptides as well as Val-NH2 had no stimulatory effect on islet glutamate dehydrogenase activity. In fact, S-(23-27), S-(24-27), and S-(25-27) inhibited the islet glutamate dehydrogenase activity, the activation by which amino acids and amino acid derivatives are known to elicit a potentiation of insulin release. Our results suggest that the C-terminal part is important to the marked potentiation of glucose-induced insulin release in vitro by secretin.

Identification of iduronate-2-sulfatase in mouse pancreatic islets

2004 ◽  
Vol 287 (5) ◽  
pp. E983-E990 ◽  
Author(s):  
I. Coronado-Pons ◽  
A. Novials ◽  
S. Casas ◽  
A. Clark ◽  
R. Gomis
Keyword(s):  
Pancreatic Islets ◽  
Cell Function ◽  
Dermatan Sulfate ◽  
Islet Cells ◽  
Secretory Response ◽  
High Rate ◽  
Insulin Content ◽  
Dependent Manner ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

The lysosomal enzyme iduronate-2-sulfatase (IDS) is expressed in pancreatic islets and is responsible for degradation of proteoglycans, such as perlecan and dermatan sulfate. To determine the role of IDS in islets, expression and regulation of the gene and localization of the enzyme were investigated in mouse pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets and β- and α-clonal cells, in which it was localized intracellularly in lysosomes. The transcriptional expression of Ids in mouse islets increased with glucose in a dose-dependent manner (11.5, 40.2, 88, and 179% at 5.5, 11.1, 16.7, and 24.4 mM, respectively, P < 0.01 for 16.7 and 24.4 mM glucose vs. 3 mM glucose). This increase was not produced by glyceraldehyde (1 mM) or 6-deoxyglucose (21.4 mM) and was blocked by the addition of mannoheptulose (21.4 mM). Neither insulin content nor secretory response to glucose (16.7 mM) was altered in mouse islets infected with lentiviral constructs carrying the IDS gene in sense orientation. Furthermore, no decrease in islet cell viability was observed in mouse islets carrying lentiviral contracts compared with controls. However, insulin content was reduced (35% vs. controls, P < 0.001) in islets infected with IDS antisense construct, while the secretory response of those islets to glucose was maintained. Inhibition of IDS by antisense infection led to an increase in lysosomal size and a high rate of insulin granule degradation via the crinophagic route in pancreatic β-cells. We conclude that IDS is localized in lysosomes in pancreatic islet cells and expression is regulated by glucose. IDS has a potential role in the normal pathway of lysosomal degradation of secretory peptides and is likely to be essential to maintain pancreatic β-cell function.

scholarly journals Concentration of adenosine 3′:5′-cyclic monophosphate in mouse pancreatic islets measured by a protein-binding radioassay

1973 ◽  
Vol 134 (2) ◽  
pp. 599-605 ◽  
Author(s):  
R. H. Cooper ◽  
S. J. H. Ashcroft ◽  
P. J. Randle
Keyword(s):  
Cyclic Amp ◽  
Protein Binding ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Release Rate ◽  
Glucose Concentration ◽  
Detectable Effect ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

A protein-binding radioassay for cyclic AMP was modified to detect less than 0.025pmol of the nucleotide. The method was applied to the measurement of cyclic AMP in small numbers of mouse pancreatic islets (as little as 25μg of tissue) by use of barium acetate–H2SO4 for deproteinization. The concentration of cyclic AMP in mouse islets incubated in media containing 3.3 or 20mm-glucose was 0.016pmol/10 islets (approx. 1μm in intracellular water). Glucose concentration (3.3 or 20mm) had no detectable effect on islet concentrations of cyclic AMP with periods of incubation or perifusion ranging from 0.5 to 60min, although insulin release rate was rapidly increased by 20mm-glucose. Caffeine (5mm) or 3-isobutyl-1-methylxanthine (1mm), which are known inhibitors of islet cyclic AMP phosphodiesterase, produced marked and rapid increases in islet cyclic AMP concentration at 3.3 or 20mm-glucose, but only enhanced the insulin release rate at the higher glucose concentration. The role of cyclic AMP in insulin release induced by glucose is discussed.

Rapid depletion of somatostatin in isolated mouse pancreatic islets after treatment with cysteamine

1985 ◽  
Vol 110 (2) ◽  
pp. 227-231 ◽  
Author(s):  
Birger Petersson ◽  
Claes Hellerström
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Basal Insulin ◽  
Glucose Stimulation ◽  
Isolated Pancreatic Islets ◽  
Basal Release ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

Abstract. Cysteamine (CSH; β-mercaptoethylamine) is known to deplete pancreatic somatostatin without affecting the insulin or glucagon content. It may therefore be useful for studies of intra-islet regulation of hormone release. In the present study injection of CSH (60 mg/kg body weight) to mice decreased the somatostatin content of their isolated pancreatic islets to 50% in 1 h and 30% in 4 h as compared to islets of non-injected controls. Exposure of isolated mouse islets to CSH (100 μg/ml) for either 0.5 h followed by incubation in control medium for 3.5 h, or continuously for 4 h, decreased the somatostatin content to about 40% of the controls. There was no change in the islet content of insulin or glucagon. Islets pretreated with CSH (100 μg/ml) for 1 h in vitro showed a decreased glucose stimulation of both oxygen consumption and glucose oxidation. Measurements of insulin release after a similar preincubation of the islets indicated an increased basal release and an attenuated glucose stimulation. It is concluded that CSH rapidly decreases islet somatostatin both in vivo and in vitro. This depletion may lead to a loss of tonic inhibition by islet somatostatin on basal insulin release. It is, however, more plausible that the increased basal insulin release reflected a direct effect of CSH on the islet β-cells.

scholarly journals Inosine-stimulated insulin release and metabolism of inosine in isolated mouse pancreatic islets

1976 ◽  
Vol 158 (2) ◽  
pp. 335-340 ◽  
Author(s):  
K Capito ◽  
C J Hedeskov
Keyword(s):  
Insulin Secretion ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Insulin Release ◽  
Lactate Production ◽  
Islet Metabolism ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated.

Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

1990 ◽  
Vol 258 (6) ◽  
pp. E975-E984 ◽  
Author(s):  
G. Z. Fadda ◽  
M. Akmal ◽  
L. G. Lipson ◽  
S. G. Massry
Keyword(s):  
Insulin Secretion ◽  
Parathyroid Hormone ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Direct Effect ◽  
Indirect Evidence ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

Sign in / Sign up

Export Citation Format

Share Document