scholarly journals Potassium ions and the secretion of insulin by islets of Langerhans incubated in vitro

1968 ◽  
Vol 108 (1) ◽  
pp. 17-24 ◽  
Author(s):  
S. L. Howell ◽  
K W Taylor
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Potassium Ions ◽  
Collagenase Digestion ◽  
Islet Tissue ◽  
Rabbit Pancreas ◽  
K Concentration

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.

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
Keyword(s):  
Insulin Release ◽  
Incubation Medium ◽  
Rabbit Pancreas ◽  
K Concentration

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+.

scholarly journals Nitric oxide inhibits, and carbon monoxide activates, islet acid α-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion

2006 ◽  
Vol 190 (3) ◽  
pp. 681-693 ◽  
Author(s):  
Henrik Mosén ◽  
Albert Salehi ◽  
Ragnar Henningsson ◽  
Ingmar Lundquist
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Insulin Secretion ◽  
Insulin Release ◽  
Islets Of Langerhans ◽  
Direct Effect ◽  
Appreciable Effect ◽  
Intact Mouse ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucoside Hydrolases

We have studied the influence of nitric oxide (NO) and carbon monoxide (CO), putative messenger molecules in the brain as well as in the islets of Langerhans, on glucose-stimulated insulin secretion and on the activities of the acid α-glucoside hydrolases, enzymes which we previously have shown to be implicated in the insulin release process. We have shown here that exogenous NO gas inhibits, while CO gas amplifies glucose-stimulated insulin secretion in intact mouse islets concomitant with a marked inhibition (NO) and a marked activation (CO) of the activities of the lysosomal/vacuolar enzymes acid glucan-1,4-α-glucosidase and acid α-glucosidase (acid α-glucoside hydrolases). Furthermore, CO dose-dependently potentiated glucose-stimulated insulin secretion in the range 0.1–1000 μM. In intact islets, the heme oxygenase substrate hemin markedly amplified glucose-stimulated insulin release, an effect which was accompanied by an increased activity of the acid α-glucoside hydrolases. These effects were partially suppressed by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Hemin also inhibited inducible NO synthase (iNOS)-derived NO production probably through a direct effect of CO on the NOS enzyme. Further, exogenous CO raised the content of both cGMP and cAMP in parallel with a marked amplification of glucose-stimulated insulin release, while exogenous NO suppressed insulin release and cAMP, leaving cGMP unaffected. Emiglitate, a selective inhibitor of α-glucoside hydrolase activities, was able to markedly inhibit the stimulatory effect of exogenous CO on both glucose-stimulated insulin secretion and the activityof acid glucan-1,4-α-glucosidase and acid α-glucosidase, while no appreciable effect on the activities of other lysosomal enzyme activities measured was found. We propose that CO and NO, both produced in significant quantities in the islets of Langerhans, have interacting regulatory roles on glucose-stimulated insulin secretion. This regulation is, at least in part, transduced through the activity of cGMP and the lysosomal/vacuolar system and the associated acid α-glucoside hydrolases, but probably also through a direct effect on the cAMP system.

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.

scholarly journals Appendix: Electron microscopy of islets Of langerhans in rabbit pancreas slices incubated in vitro

1967 ◽  
Vol 102 (3) ◽  
pp. 928-1928 ◽  
Author(s):  
J. R. Williamson ◽  
P.E. Lacy ◽  
K. W. Taylor
Keyword(s):  
Electron Microscopy ◽  
Islets Of Langerhans ◽  
Rabbit Pancreas

scholarly journals Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway

2001 ◽  
pp. 667-675 ◽  
Author(s):  
J Westerlund ◽  
H Ortsater ◽  
F Palm ◽  
T Sundsten ◽  
P Bergsten
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Prolonged Exposure ◽  
Pulse Frequency ◽  
Secretory Rate ◽  
Pulsatile Release ◽  
Glucose Signaling ◽  
K Concentration ◽  
Channel Dependent ◽  
Glucose Stimulated Insulin Secretion

OBJECTIVE: Regulation of insulin release by glucose involves dual pathways, including or not inhibition of ATP-sensitive K(+) channels (K(ATP) channels). Whereas the K(ATP) channel-dependent pathway produces pulsatile release of insulin it is not clear whether the independent pathway also generates such kinetics. DESIGN AND METHODS: To clarify this matter, insulin secretion and cytoplasmic Ca(2+) ([Ca(2+)](i)) were studied in perifused pancreatic islets from ob/ob mice. Insulin release was measured by ELISA technique and [Ca(2+)](i) by dual-wavelength fluorometry. RESULTS: Insulin secretion was pulsatile (0.2--0.3/min) at 3 mmol/l glucose when [Ca(2+)](i) was low and stable. Stimulation with 11 mmol/l of the sugar increased the amplitude of the insulin pulses with maintained frequency and induced oscillations in [Ca(2+)](i). Permanent opening of the K(ATP) channels with diazoxide inhibited glucose-stimulated insulin secretion back to basal levels with maintained pulsatility despite stable and basal [Ca(2+)](i) levels. Increase of the K(+) concentration to 30.9 mmol/l in the continued presence of diazoxide and 11 mmol/l glucose restored the secretory rate with maintained pulsatility and caused stable elevation in [Ca(2+)](i). Simultaneous introduction of diazoxide and elevation of K(+) augmented average insulin release almost 30-fold in 3 mmol/l glucose with maintained pulse frequency. Subsequent elevation of the glucose concentration to 11 and 20 mmol/l increased the release levels. After prolonged exposure to diazoxide, elevated K(+) and 20 mmol/l glucose, the pulse frequency decreased significantly. CONCLUSIONS: Not only glucose signaling via the K(ATP) channel-dependent but also that via the independent pathway generates amplitude-modulated pulsatile release of insulin from isolated islets.

Effect of gestational hyperglycemia on insulin secretion in vivo and in vitro by fetal rat pancreas

1986 ◽  
Vol 251 (1) ◽  
pp. E86-E91 ◽  
Author(s):  
M. T. Bihoreau ◽  
A. Ktorza ◽  
A. Kervran ◽  
L. Picon
Keyword(s):  
Insulin Secretion ◽  
B Cell ◽  
Insulin Release ◽  
Plasma Insulin ◽  
Cell Function ◽  
Pregnant Rats ◽  
Fetal Rat ◽  
Gestational Hyperglycemia

The effects of gestational hyperglycemia on B-cell function were studied in near-term fetuses from unrestrained pregnant rats made slightly or highly hyperglycemic using continuous glucose infusion during the last week of pregnancy. Pancreatic and plasma insulin and insulin secretion in vitro were studied in the fetuses. Compared with controls, slightly hyperglycemic fetuses showed increased pancreatic and plasma insulin concentrations and similar insulin release in response to glucose in vitro. In highly hyperglycemic fetuses, pancreatic and plasma insulin concentrations were unchanged compared with controls, and insulin release in vitro was insensitive to glucose and to the mixture glucose plus theophylline. These results confirm that glucose is able to stimulate insulin secretion in normal or slightly hyperglycemic fetuses and suggest that severe hyperglycemia per se, without association of other metabolic disorders or toxic injuries, profoundly alters the stimulus-secretion coupling of the fetal rat B-cell.

THE STIMULATION OF INSULIN RELEASE BY ESSENTIAL AMINO ACIDS FROM RABBIT PANCREAS IN VITRO

1970 ◽  
Vol 47 (3) ◽  
pp. 347-356 ◽  
Author(s):  
R. D. G. MILNER
Keyword(s):  
Amino Acids ◽  
Insulin Release ◽  
Incubation Medium ◽  
Statistical Significance ◽  
Adenosine Monophosphate ◽  
Essential Amino Acids ◽  
Isoleucine Leucine ◽  
Rabbit Pancreas

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.

THE SECRETION OF INSULIN FROM FOETAL AND POSTNATAL RABBIT PANCREAS IN VITRO IN RESPONSE TO VARIOUS SUBSTANCES

1969 ◽  
Vol 44 (2) ◽  
pp. 267-272 ◽  
Author(s):  
R. D. G. MILNER
Keyword(s):  
Insulin Secretion ◽  
Incubation Medium ◽  
Β Cell ◽  
Functional Competence ◽  
Stimulate Insulin Secretion ◽  
Rabbit Pancreas ◽  
Foetal Pancreas

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.

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