Inhibition by mepacrine and p-bromophenacylbromide of phosphoinositide hydrolysis, glucose oxidation, calcium uptake and insulin release in rat pancreatic islets

1984 ◽  
Vol 33 (16) ◽  
pp. 2657-2662 ◽  
Author(s):  
L. Best ◽  
A. Sener ◽  
P.C.F. Mathias ◽  
W.J. Malaisse
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Calcium Uptake ◽  
Phosphoinositide Hydrolysis ◽  
Rat Pancreatic Islets

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.

scholarly journals Nutrient Augmentation of Ca2+-Dependent and Ca2+-Independent Pathways in Stimulus-Coupling to Insulin Secretion Can Be Distinguished by Their Guanosine Triphosphate Requirements: Studies on Rat Pancreatic Islets*

Endocrinology ◽  
1998 ◽  
Vol 139 (3) ◽  
pp. 1172-1183 ◽  
Author(s):  
Mitsuhisa Komatsu ◽  
Mitsuhiko Noda ◽  
Geoffrey W. G. Sharp
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Current Knowledge ◽  
Inhibitory Effect ◽  
Salvage Pathway ◽  
Rat Pancreatic Islets ◽  
Simultaneous Activation ◽  
Underlying Mechanisms

To delineate the underlying mechanisms by which glucose augments both Ca2+-dependent and Ca2+-independent insulin release, the latter induced by the simultaneous activation of protein kinases A and C, we examined the effects of GTP depletion by mycophenolic acid (MPA), an inhibitor of GTP synthesis, on the augmentation of insulin release from rat pancreatic islets. MPA treatment reduced GTP content by 30–40% and completely abolished glucose-induced augmentation of Ca2+-independent insulin release. Thus, this pathway is extremely sensitive to a decrease in cellular GTP content. Complete inhibition was also observed in islets treated with MPA plus adenine, to maintain ATP levels, under which conditions GTP is selectively depleted. Provision of guanine, which increases the activity of a salvage pathway for GTP synthesis and normalizes GTP content, completely reversed the inhibitory effect of MPA. Neither glucose utilization nor glucose oxidation was affected by MPA. The augmentation of Ca2+-independent insulin release by several other metabolizable nutrients including α-ketoisocaproic acid (KIC) was also inhibited by MPA. In sharp contrast, augmentation of Ca2+-dependent insulin release by KIC was resistant to GTP depletion, indicating that nutrient-induced augmentation of the Ca2+-dependent- and Ca2+-independent secretory pathways can be differentiated by GTP dependency. We interpret these data in accord with current knowledge concerning the two known stimuli for exocytosis, Ca2+ and GTP (independently of Ca2+). We propose that both Ca2+-dependent and Ca2+-independent augmentation occurs via one metabolic pathway acting upon Ca2+- and upon GTP-stimulated exocytosis. Activation of PKA and PKC stimulates the GTP-sensitive exocytosis.

Effect of CCK-8 on pentose phosphate shunt activity, pyridine nucleotides, and glucokinase of rat islets

1989 ◽  
Vol 256 (1) ◽  
pp. E68-E73 ◽  
Author(s):  
E. J. Verspohl ◽  
I. Breuning ◽  
H. P. Ammon
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Pentose Phosphate ◽  
Dependent Manner ◽  
Hexokinase Activity ◽  
Rat Pancreatic Islets ◽  
Pentose Phosphate Shunt

In rat pancreatic islets the effects of cholecystokinin octapeptide (CCK-8) on pentose phosphate shunt (PPS) activity, glucokinase and hexokinase activity, and NADPH, NADP+, NADH, and NAD+ were studied. By elevating the glucose concentration from 3.0 to 8.3 and 16.7 mM the oxidation of [1-14C]- and [6-14C]glucose and the calculated PPS activity were increased in a concentration-dependent manner; 10 nM CCK-8 enhanced selectively the effect on [1-14C]glucose oxidation thereby increasing the PPS activity but only at an intermediate glucose concentration (8.3 mM). CCK-8 had no effect on glucokinase or hexokinase activity and CCK-8 did not influence glucose utilization. By elevating the glucose concentration, total NADPH and NADH were increased and total NADP+ and NAD+ were decreased. CCK-8 (10 nM) increased selectively NADPH and decreased NADP+ but did not change NADH or NAD+; the effect of CCK-8 on NADPH and NADH was only observed in the presence of an intermediate stimulatory glucose concentration (8.3 mM) but not at either a substimulatory glucose concentration or a maximally stimulatory glucose concentration for insulin release (3.0 or 16.7 mM). The data indicate first that CCK-8 does not act on glucose phosphorylation or glucose utilization and second that CCK-8 increases PPS activity and NADPH levels in rat pancreatic islets. Since the concentrations of glucose necessary for these CCK-8 effects are in the range of 8.3 mM and parallel with those necessary for insulin release as shown in earlier observations, glucose oxidation via pentose phosphate shunt and NADPH are suggested to be related to the CCK-8-modulated insulin release.

A Possible Role of Intracellular and Membrane Thiols of Rat Pancreatic Islets in Calcium Uptake and Insulin Release*

Endocrinology ◽  
1983 ◽  
Vol 112 (2) ◽  
pp. 720-726 ◽  
Author(s):  
HERMANN P. T. AMMON ◽  
ROLF HÄGELE ◽  
NABIL YOUSSIF ◽  
ROSLINDIS EUJEN ◽  
NAJIBA EL-AMRI
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Calcium Uptake ◽  
Rat Pancreatic Islets

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.

Role for GTP in glucose-induced phospholipase C activation in pancreatic islets

1996 ◽  
Vol 271 (1) ◽  
pp. E85-E95 ◽  
Author(s):  
J. Vadakekalam ◽  
M. E. Rabaglia ◽  
Q. H. Chen ◽  
S. A. Metz
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Phospholipase C ◽  
Insulin Release ◽  
Mycophenolic Acid ◽  
Phosphoinositide Hydrolysis ◽  
Intact Cells ◽  
Rat Islets ◽  
First Time ◽  
Permissive Role

We have previously demonstrated a permissive role for GTP in insulin secretion; in the current studies, we examined the effect of GTP on phospholipase C (PLC) activation to explore one possible mechanism for that observation. In rat islets preexposed to the GTP synthesis inhibitors mycophenolic acid (MPA) or mizoribine (MZ), PLC activation induced by 16.7 mM glucose (or by 20 mM alpha-ketoisocaproic acid) was inhibited 63% without altering the labeling of phosphoinositide substrates. Provision of guanine, which normalizes islet GTP content and insulin release, prevented the inhibition of PLC by MPA. Glucose-induced phosphoinositide hydrolysis was blocked by removal of extracellular Ca2+ or by diazoxide. PLC induced directly by Ca2+ influx (i.e., 40 mM K+) was reduced 42% in MPA-pretreated islets but without inhibition of the concomitant insulin release. These data indicate that glucose-induced PLC activation largely reflects Ca2+ entry and demonstrate (for the first time in intact cells) that adequate GTP is necessary for glucose (and Ca(2+)-)-induced PLC activation but not for maximal Ca(2+)-induced exocytosis.

Sensitivity to Cd2+ but resistance to Ni2+ of Ca2+ inflow into rat pancreatic islets

1990 ◽  
Vol 258 (3) ◽  
pp. E529-E533 ◽  
Author(s):  
P. O. Plasman ◽  
M. Hermann ◽  
A. Herchuelz ◽  
P. Lebrun
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Islet Cells ◽  
Excitable Cells ◽  
45Ca Uptake ◽  
Rat Pancreatic Islets ◽  
Cell Plasma ◽  
Different Types ◽  
45Ca Efflux ◽  
Ca2 Channels

The presence of different types [long lasting (L) and transient (T)] of active voltage-operated Ca2+ channels in islet cells was investigated by comparing the effects of Cd2+, Ni2+, and 1,4-dihydropyridines on 45Ca uptake, 45Ca efflux, and insulin release in intact rat pancreatic islets. In several other excitable cells the L-channel has been shown to be modulated by 1,4-dihydropyridines and Cd2+, whereas the T-channel was reported to be sensitive to Ni2+. Nifedipine and Cd2+ inhibited whereas BAY K 8644 enhanced the glucose (11.1, 22.2 mM)-stimulated short-term 45Ca uptake, 45Ca efflux, and insulin release. In contrast, the stimulatory effects of glucose (11.1, 22.2 mM) on 45Ca uptake, 45Ca efflux, and insulin release were unaffected by Ni2+. These findings confirm that glucose provokes Ca2+ entry mainly by activating voltage-sensitive Ca2+ channels of the L-type and suggest that the B-cell plasma membrane is not equipped with active T-type Ca2+ channels.

scholarly journals Insulin release and arachidonic acid metabolism in neonatal rat pancreatic islets. (2)

1984 ◽  
Vol 36 ◽  
pp. 96
Author(s):  
Naoko Tanaka ◽  
Shohei Nagawa ◽  
Keiko Murakoso ◽  
Kunio Haito ◽  
Shizuo Shimizu ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Neonatal Rat ◽  
Rat Pancreatic Islets
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