INSULIN RELEASE FROM HUMAN FOETAL PANCREAS IN RESPONSE TO GLUCOSE, LEUCINE AND ARGININE

1972 ◽  
Vol 52 (3) ◽  
pp. 497-505 ◽  
Author(s):  
R. D. G. MILNER ◽  
M. A. ASHWORTH ◽  
A. J. BARSON
Keyword(s):  
Body Weight ◽  
Insulin Release ◽  
Basal Insulin ◽  
Exocrine Pancreas ◽  
Significant Rise ◽  
Free Medium ◽  
Β Cell ◽  
Foetal Pancreas ◽  
Human Foetuses

SUMMARY Pieces of pancreas from human foetuses of 14–24 weeks gestational age and weighing between 50 and 625 g were incubated in vitro. Insulin release was studied under control conditions and in media supplemented with glucose (3 mg/ml), leucine (5 mmol/1) or arginine (5 mmol/1). Glucose never caused a significant rise in insulin release from the pancreas. The failure of mannoheptulose (3 mg/ml) and 2-deoxyglucose (3 mg/ml) to suppress basal insulin release in a glucose-free medium indicated that basal insulin release was not governed by the liberation of glucose from glycogen in the exocrine pancreas. Arginine stimulated insulin release in four experiments using pancreas from foetuses weighing more than 200 g, but failed to cause insulin release from the pancreas of foetuses weighing less than 200 g in three experiments. Leucine consistently stimulated insulin release from the pancreas of foetuses of less than 200 g body weight but was only variably effective in causing insulin release from pancreas of foetuses weighing more than 200 g. The experimental results illustrate the development of different mechanisms for the release of insulin from the human foetal β cell.

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.

Myosin light-chain phosphorylation controls insulin secretion at a proximal step in the secretory cascade

1997 ◽  
Vol 273 (4) ◽  
pp. E782-E789 ◽  
Author(s):  
Yuji Iida ◽  
Takao Senda ◽  
Yoshihisa Matsukawa ◽  
Koji Onoda ◽  
Jun-Ichi Miyazaki ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Secretory Granules ◽  
Cam Kinase Ii ◽  
Cam Kinase ◽  
Β Cell ◽  
Cell Extracts

The aim of this study was to investigate how insulin secretion is controlled by phosphorylation of the myosin light chain (MLC). Ca2+-evoked insulin release from pancreatic islets permeabilized with streptolysin O was inhibited by different monoclonal antibodies against myosin light-chain kinase (MLCK) to an extent parallel to their inhibition of purified MLCK. Anti-MLCK antibody also inhibited insulin release caused by the stable GTP analog guanosine 5′- O-(3-thiodiphosphate), even at a substimulatory concentration (0.1 μM) of Ca2+. Free Ca2+ increased MLC peptide phosphorylation by β-cell extracts in vitro. In contrast to the phosphorylation by purified MLCK or by calmodulin (CaM) kinase II, the activity partially remained with the β-cell under nonstimulatory Ca2+ (0.1 μM) conditions. The MLCK inhibitor ML-9 inhibited the activity in the β-cell with both substimulatory and stimulatory Ca2+, whereas KN-62, an inhibitor of CaM kinase II, only exerted an influence in the latter case. ML-9 decreased intracellular granule movement in MIN6 cells under basal and acetylcholine-stimulated conditions. We propose that MLC phosphorylation may modulate translocation of secretory granules, resulting in enhanced insulin secretion.

Sustained exposure of toxically damaged mouse pancreatic islets to high glucose does not increase β-cell dysfunction

1989 ◽  
Vol 123 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. L. Eizirik ◽  
S. Sandler
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
High Glucose ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Stimulation ◽  
Cell Dysfunction ◽  
Mouse Pancreatic Islets ◽  
Insulin Secretory Response

ABSTRACT The aim of this study was to clarify whether prolonged in-vitro exposure of either normal or damaged β cells to a high glucose environment can be toxic to these cells. For this purpose NMRI mice were injected intravenously with a diabetogenic dose of streptozotocin (SZ; 160 mg/kg) or vehicle alone (controls). Their islets were isolated 15 min after the injection and subsequently maintained in culture for 21 days in the presence of 11·1 or 28 mmol glucose/l. After this period, during acute glucose stimulation, the control islets showed a marked increase in their insulin release in response to a high glucose stimulus. In the SZ-exposed islets there was a decrease in DNA and insulin contents, and a deficient insulin secretory response to glucose. However, in the SZ-damaged islets as well as in the control islets, culture with 28 mmol glucose/l compared with 11·1 mmol glucose/l did not impair islet retrieval after culture, islet DNA content or glucose-induced insulin release. Thus, the degree of damage was similar in the SZ-treated islets cultured at the two concentrations of glucose. These results suggest that glucose is not toxic to normal or damaged mouse pancreatic islets over a prolonged period in tissue culture. Journal of Endocrinology (1989) 123, 47–51

scholarly journals CK2 acts as a potent negative regulator of receptor-mediated insulin release in vitro and in vivo

2015 ◽  
Vol 112 (49) ◽  
pp. E6818-E6824 ◽  
Author(s):  
Mario Rossi ◽  
Inigo Ruiz de Azua ◽  
Luiz F. Barella ◽  
Wataru Sakamoto ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Insulin Release ◽  
Cell Activity ◽  
Negative Regulator ◽  
Whole Body ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Release In Vitro

G protein-coupled receptors (GPCRs) regulate virtually all physiological functions including the release of insulin from pancreatic β-cells. β-Cell M3 muscarinic receptors (M3Rs) are known to play an essential role in facilitating insulin release and maintaining proper whole-body glucose homeostasis. As is the case with other GPCRs, M3R activity is regulated by phosphorylation by various kinases, including GPCR kinases and casein kinase 2 (CK2). At present, it remains unknown which of these various kinases are physiologically relevant for the regulation of β-cell activity. In the present study, we demonstrate that inhibition of CK2 in pancreatic β-cells, knockdown of CK2α expression, or genetic deletion of CK2α in β-cells of mutant mice selectively augmented M3R-stimulated insulin release in vitro and in vivo. In vitro studies showed that this effect was associated with an M3R-mediated increase in intracellular calcium levels. Treatment of mouse pancreatic islets with CX4945, a highly selective CK2 inhibitor, greatly reduced agonist-induced phosphorylation of β-cell M3Rs, indicative of CK2-mediated M3R phosphorylation. We also showed that inhibition of CK2 greatly enhanced M3R-stimulated insulin secretion in human islets. Finally, CX4945 treatment protected mice against diet-induced hyperglycemia and glucose intolerance in an M3R-dependent fashion. Our data demonstrate, for the first time to our knowledge, the physiological relevance of CK2 phosphorylation of a GPCR and suggest the novel concept that kinases acting on β-cell GPCRs may represent novel therapeutic targets.

Insulin Release from Human Foetal Pancreas in Vitro

1971 ◽  
Vol 3 (05) ◽  
pp. 353-354 ◽  
Author(s):  
R. Milner ◽  
M. Ashworth ◽  
A. Barson
Keyword(s):  
Insulin Release ◽  
Foetal Pancreas

DEVELOPMENT OF PATHWAYS OF INSULIN SECRETION IN THE RABBIT

1975 ◽  
Vol 64 (2) ◽  
pp. 349-361 ◽  
Author(s):  
R. D. G. MILNER ◽  
F. N. LEACH ◽  
M. A. ASHWORTH ◽  
A. CSER ◽  
P. M. B. JACK
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Similar Rate ◽  
Extracellular Glucose ◽  
Cell Changes ◽  
Foetal Pancreas ◽  
Stimulation Of

SUMMARY Insulin release was studied in vitro using pieces of pancreas from rabbits of between 24 days gestational age and 6 weeks postnatal age. When allowance was made for the fraction of pancreas which was endocrine, 16·5 mm-glucose caused increasing stimulation of insulin release as development advanced and 3·3 mm-glucose caused a similar rate of secretion at all ages. Secretion was not significantly influenced by insulin destruction in the incubation medium. Glucagon (5 μg/ml) did not stimulate insulin secretion from 24-day foetal pancreas but did so postnatally. Theophylline (1 mmol/l) stimulated insulin release at all ages and was equipotent on 24-day foetal pancreas in 3·3 or 16·5 mm-glucose. The stimulation of insulin release from 24-day foetal pancreas by 1 mm-theophylline occurred in the absence of extracellular glucose, pyruvate, fumarate and glutamate and in the presence of mannoheptulose and 2-deoxyglucose (each 3 mg/ml). Adrenaline (1 μmol/l) and diazoxide (250 μg/ml) abolished or attenuated the stimulation of insulin release by glucose, leucine plus arginine or theophylline from 24-day foetal, 1 day and 6 weeks postnatal pancreas. The stimulation of insulin release from 6-week-old pancreas by 1 mm-barium was blocked by adrenaline and diazoxide but the effect became less with increasing immaturity. The experimental results illustrate some of the ways in which insulin secretion by the rabbit β cell changes as a function of development and draw attention to the importance of glucose and cyclic adenosine monophosphate in this process.

Stevioside does not cause increased basal insulin secretion or β-cell desensitization as does the sulphonylurea, glibenclamide: Studies in vitro

Life Sciences ◽  
2006 ◽  
Vol 78 (15) ◽  
pp. 1748-1753 ◽  
Author(s):  
Jianguo Chen ◽  
Per Bendix Jeppesen ◽  
Reziwanggu Abudula ◽  
Stig E.U. Dyrskog ◽  
Michele Colombo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Β Cell ◽  
Basal Insulin Secretion

scholarly journals Effects of organic mercurials on mammalian pancreatic β-cells. Insulin release, glucose transport, glucose oxidation, membrane permeability and ultrastructure

1972 ◽  
Vol 129 (2) ◽  
pp. 241-254 ◽  
Author(s):  
Gunnar D. Bloom ◽  
Bo Hellman ◽  
Lars-Åke Idahl ◽  
Åke Lernmark ◽  
Janove Sehlin ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Glucose Transport ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Sulphonic Acid ◽  
Β Cells ◽  
Β Cell ◽  
Cell Plasma ◽  
Organic Mercurials

The effects of p-chloromercuribenzoic acid and chloromercuribenzene-p-sulphonic acid on pancreatic islets were studied in vitro. Obese–hyperglycaemic mice were used as the source of microdissected islets containing more than 90% β-cells. p-Chloromercuribenzoic acid and chloromercuribenzene-p-sulphonic acid stimulated insulin release at concentrations of 0.01mm or above. This stimulation was significantly inhibited by the omission of Ca2+or the addition of adrenaline, diazoxide or 2,4-dinitrophenol. p-Chloromercuribenzoic acid or chloromercuribenzene-p-sulphonic acid did not interfere with the insulin-releasing ability of glucose. Micro-perifusion experiments revealed that the release of insulin in response to organic mercurial occurred almost instantaneously, was reversible, and was biphasic. The two mercurials inhibited glucose transport as well as glucose oxidation, and increased the mannitol and sucrose spaces of isolated islets. Compared with the effects on insulin release, those on glucose transport and membrane permeability were characterized by a longer latency and/or required higher concentrations of organic mercurial. Apart from a seemingly higher proportion of β-cells exhibiting certain degenerative features, in islets exposed to 0.1mm-chloromercuribenzene-p-sulphonic acid for 60min, no significant differences with respect to β-cell fine structure were noted between non-incubated islets and islets incubated with chloromercuribenzene-p-sulphonic acid or glucose or both. It is suggested that insulin release may be regulated by relatively superficial thiol groups in the β-cell plasma membrane.

HUMAN FOETAL PANCREATIC INSULIN SECRETION IN RESPONSE TO IONIC AND OTHER STIMULI

1971 ◽  
Vol 51 (2) ◽  
pp. 323-332 ◽  
Author(s):  
R. D. G. MILNER ◽  
A. J. BARSON ◽  
M. A. ASHWORTH
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Β Cells ◽  
Pancreatic Insulin ◽  
Foetal Life ◽  
Acinar Tissue ◽  
Foetal Pancreas

SUMMARY Pieces of human foetal pancreas were incubated under control conditions and in media containing different stimuli of insulin release. Insulin secretion was stimulated from the pancreases of foetuses (83–625 g body weight) which were of 16–24 weeks gestational age. Potassium (60 mmol/l), barium (2·54 mmol/l) and ouabain (10−5 mol/l) were effective stimuli in all experiments. Glucagon (5 μg/ml), theophylline (1 mmol/l) and dibutyryl 3′,5′-cyclic adenosine monophosphate (1 mmol/l) stimulated insulin secretion in media containing 0, 0·6 or 3·0 mg glucose/ml. Theophylline and dibutyryl 3′,5′-cyclic adenosine monophosphate were effective in all experients and glucagon stimulated insulin release in four out of six experiments. At all ages studied, histological examination of the pancreas after each experiment revealed islets of Langerhans containing β cells. In most cases the islets were of the mantle type but occasionally bipolar islets were seen. Cellular normality, as judged by light microscopy, was preserved after periods of incubation for up to 5½ h. Glycogen was demonstrable in the pancreatic acinar tissue but not in the islets. The results of these experiments indicate that, between the 16th and 24th week of foetal life, the human β cell is capable of releasing insulin in vitro when stimulated appropriately.

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