Stimulation of insulin secretion from mouse pancreatic islets, maintained in tissue culture, by the pituitary neurointermediate lobe of the genetically obese mouse (obob)

1980 ◽  
Vol 95 (2) ◽  
pp. 792-795 ◽  
Author(s):  
Anne Beloff-Chain ◽  
N. Billingham ◽  
M.A. Cawthorne
Keyword(s):  
Tissue Culture ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Obese Mouse ◽  
Neurointermediate Lobe ◽  
Mouse Pancreatic Islets ◽  
Stimulation Of

scholarly journals Cytosolic ratios of free [NADPH]/[NADP+] and [NADH]/[NAD+] in mouse pancreatic islets, and nutrient-induced insulin secretion

1987 ◽  
Vol 241 (1) ◽  
pp. 161-167 ◽  
Author(s):  
C J Hedeskov ◽  
K Capito ◽  
P Thams
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Coupling Factor ◽  
Mouse Pancreatic Islets ◽  
Cell Depolarization ◽  
K Permeability ◽  
Cell Glucose ◽  
Stimulation Of

When the extracellular concentration of glucose was raised from 3 mM to 7 mM (the concentration interval in which beta-cell depolarization and the major decrease in K+ permeability occur), the cytosolic free [NADPH]/[NADP+] ratio in mouse pancreatic islets increased by 29.5%. When glucose was increased to 20 mM, a 117% increase was observed. Glucose had no effect on the cytosolic free [NADH]/[NAD+] ratio. Neither the cytosolic free [NADPH]/[NADP+] ratio nor the corresponding [NADH]/[NAD+] ratio was affected when the islets were incubated with 20 mM-fructose or with 3 mM-glucose + 20 mM-fructose, although the last-mentioned condition stimulated insulin release. The insulin secretagogue leucine (10 mM) stimulated insulin secretion, but lowered the cytosolic free [NADPH]/[NADP+] ratio; 10 mM-leucine + 10 mM-glutamine stimulated insulin release and significantly enhanced both the [NADPH]/[NADP+] ratio and the [NADH]/[NAD+] ratio. It is concluded that the cytosolic free [NADPH]/[NADP+] ratio may be involved in coupling beta-cell glucose metabolism to beta-cell depolarization and ensuing insulin secretion, but it may not be the sole or major coupling factor in nutrient-induced stimulation of insulin secretion.

scholarly journals GPRC6A Mediates the Effects of l-Arginine on Insulin Secretion in Mouse Pancreatic Islets

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4608-4615 ◽  
Author(s):  
Min Pi ◽  
Yunpeng Wu ◽  
Nataliya I Lenchik ◽  
Ivan Gerling ◽  
L. Darryl Quarles
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Ex Vivo ◽  
Β Cells ◽  
Direct Role ◽  
Mouse Pancreatic Islets ◽  
Islet Size ◽  
G Protein Coupled ◽  
Stimulation Of

Abstract l-Arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism whereby it stimulates insulin secretion from β-cells is not known. The possibility that l-Arg regulates insulin secretion through a G protein-coupled receptor (GPCR)-mediated mechanism is suggested by the high expression of the nutrient receptor GPCR family C group 6 member A (GPRC6A) in the pancreas and TC-6 β-cells and the finding that Gprc6a−/]minus] mice have abnormalities in glucose homeostasis. To test the direct role of GPRC6A in regulating insulin secretion, we evaluated the response of pancreatic islets derived from Gprc6a−/]minus] mice to l-Arg. We found that the islet size and insulin content were decreased in pancreatic islets from Gprac6a−/]minus] mice. These alterations were selective for β-cells, because there were no abnormalities in serum glucagon levels or glucagon content of islets derived from Gprac6a−/]minus] mice. Significant reduction was observed in both the pancreatic ERK response to l-Arg administration to Gprc6a−/]minus] mice in vivo and l-Arg-induced insulin secretion and production ex vivo in islets isolated from Gprc6a−/]minus] mice. l-Arg stimulation of cAMP accumulation in isolated islets isolated from Gprc6a−/]minus] mice was also diminished. These findings suggest that l-Arg stimulation of insulin secretion in β-cells is mediated, at least in part, through GPRC6A activation of cAMP pathways.

scholarly journals An inhibitory role for polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets

1986 ◽  
Vol 237 (1) ◽  
pp. 131-138 ◽  
Author(s):  
P Thams ◽  
K Capito ◽  
C J Hedeskov
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Kinase C ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets ◽  
Protein Kinase C Activation ◽  
Stimulation Of

The occurrence and function of polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets were studied. Determination of polyamines in mouse islets revealed 0.9 +/- 0.3 (mean +/- S.E.M., n = 6) pmol of putrescine, 11.7 +/- 3.2 (8) pmol of spermidine and 3.7 +/- 0.6 (8) pmol of spermine per islet, corresponding to intracellular concentrations of 0.3-0.5 mM-putrescine, 3.9-5.9 mM-spermidine and 1.2-1.9 mM-spermine in mouse islets. Stimulation of insulin secretion by glucose, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) or the sulphonylurea glibenclamide did not affect these polyamine contents. In accordance with a role for protein kinase C in insulin secretion, TPA stimulated both protein kinase C activity and insulin secretion. Stimulation of insulin secretion by TPA was dependent on a non-stimulatory concentration of glucose and was further potentiated by stimulatory concentrations of glucose, glibenclamide or 3-isobutyl-1-methylxanthine, suggesting that protein kinase C activation, Ca2+ mobilization and cyclic AMP accumulation are all needed for full secretory response of mouse islets. Spermidine (5 mM) and spermine (1.5 mM) at concentrations found in islets inhibited protein kinase C stimulated by TPA + phosphatidylserine by 55% and 45% respectively. Putrescine (0.5 mM) was without effect, but inhibited the enzyme at higher concentrations (2-10 mM). Inhibition of protein kinase C by polyamines showed competition with Ca2+, and Ca2+ influx in response to glucose or glibenclamide prevented inhibition of insulin secretion by exogenous polyamines at concentrations where they did not affect glucose oxidation. It is suggested that inhibition of protein kinase C by polyamines may be of significance for regulation of insulin secretion in vivo and that Ca2+ influx may function by displacing inhibitory polyamines bound to phosphatidylserine in membranes.

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 Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+handling in mouse pancreatic islets

2010 ◽  
Vol 104 (8) ◽  
pp. 1148-1155 ◽  
Author(s):  
Rosane A. Ribeiro ◽  
Emerielle C. Vanzela ◽  
Camila A. M. Oliveira ◽  
Maria L. Bonfleur ◽  
Antonio C. Boschero ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Phospholipase C ◽  
Islet Cells ◽  
Taurine Supplementation ◽  
Adult Mice ◽  
Intracellular Ca ◽  
Mouse Pancreatic Islets ◽  
Methyl Xanthine

Taurine (TAU) supplementation increases insulin secretion in response to high glucose concentrations in rodent islets. This effect is probably due to an increase in Ca2+handling by the islet cells. Here, we investigated the possible involvement of the cholinergic/phospholipase C (PLC) and protein kinase (PK) A pathways in this process. Adult mice were fed with 2 % TAU in drinking water for 30 d. The mice were killed and pancreatic islets isolated by the collagenase method. Islets from TAU-supplemented mice showed higher insulin secretion in the presence of 8·3 mm-glucose, 100 μm-carbachol (Cch) and 1 mm-3-isobutyl-1-methyl-xanthine (IBMX), respectively. The increase in insulin secretion in response to Cch in TAU islets was accompanied by a higher intracellular Ca2+mobilisation and PLCβ2protein expression. The Ca2+uptake was higher in TAU islets in the presence of 8·3 mm-glucose, but similar when the islets were challenged by glucose plus IBMX. TAU islets also showed an increase in the expression of PKAα protein. This protein may play a role in cation accumulation, since the amount of Ca2+in these islets was significantly reduced by the PKA inhibitors:N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H89) and PK inhibitor-(6–22)-amide (PKI). In conclusion, TAU supplementation increases insulin secretion in response to glucose, favouring both influx and internal mobilisation of Ca2+, and these effects seem to involve the activation of both PLC–inositol-1,4,5-trisphosphate and cAMP–PKA pathways.

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.

scholarly journals Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets

1987 ◽  
Vol 248 (1) ◽  
pp. 109-115 ◽  
Author(s):  
J Sehlin
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Calcium Uptake ◽  
Maximum Effect ◽  
Mouse Pancreatic Islets ◽  
Stimulus Secretion Coupling ◽  
Ca2 Channels

Microdissected beta-cell-rich pancreatic islets of non-inbred ob/ob mice were used in studies of how perchlorate (CIO4-) affects stimulus-secretion coupling in beta-cells. CIO4- at 16 mM potentiated D-glucose-induced insulin release, without inducing secretion at non-stimulatory glucose concentrations. The potentiation mainly applied to the first phase of stimulated insulin release. In the presence of 20 mM-glucose, the half-maximum effect of CIO4- was reached at 5.5 mM and maximum effect at 12 mM of the anion. The potentiation was reversible and inhibitable by D-mannoheptulose (20 mM) or Ca2+ deficiency. CIO4- at 1-8 mM did not affect glucose oxidation. The effects on secretion were paralleled by a potentiation of glucose-induced 45Ca2+ influx during 3 min. K+-induced insulin secretion and 45Ca2+ uptake were potentiated by 8-16 mM-CIO4-. The spontaneous inactivation of K+-induced (20.9 mM-K+) insulin release was delayed by 8 mM-CIO4-. The anion potentiated the 45Ca2+ uptake induced by glibenclamide, which is known to depolarize the beta-cell. Insulin release was not affected by 1-10 mM-trichloroacetate. It is suggested that CIO4- stimulates the beta-cell by affecting the gating of voltage-controlled Ca2+ channels.

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