Stimulation of insulin release from pancreatic islets by quinones

1991 ◽  
Vol 11 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Michael J. MacDonald
Keyword(s):  
Insulin Release ◽  
Channel Blocker ◽  
Coenzyme Q ◽  
Quinone Reductase ◽  
Second Phase ◽  
Antimycin A ◽  
Free Medium ◽  
Insulin Secretagogues ◽  
Stimulate Insulin Release ◽  
Stimulation Of

Coenzyme Q (CoQ0) and other quinones were shown to be potent insulin secretagogues in the isolated pancreatic islet. The order of potency was CoQ0≅benzoquinone≅hydroquinonemenadione. CoQ6 and CoQ10 (ubiquinone), duroquinone and durohydroquinone did not stimulate insulin release. CoQ0's insulinotropism was enhanced in calcium-free medium and CoQ0 appeared to stimulate only the second phase of insulin release. CoQ0 inhibited inositol mono-, bis- and trisphosphate formation. Inhibitors of mitochondrial respiration (rotenone, antimycin A, FCCP and cyanide) and the calcium channel blocker verapamil, did not inhibit CoQ0-induced insulin release. Dicumarol, an inhibitor of quinone reductase, did not inhibit CoQ0-induced insulin release, but it did inhibit glucose-induced insulin release suggesting that the enzyme and quinones play a role in glucose-induced insulin release. Quinones may stimulate insulin release by mimicking physiologically-occuring quinones, such as CoQ10, by acting on the plasma membrane or in the cytosol. Exogenous quinones may bypass the quinone reductase reaction, as well as many reactions important for exocytosis.

Effect of galanin on glucose-, arginine-, or potassium-stimulated insulin release

1989 ◽  
Vol 256 (5) ◽  
pp. E619-E623
Author(s):  
T. Yoshimura ◽  
J. Ishizuka ◽  
G. H. Greeley ◽  
J. C. Thompson
Keyword(s):  
Insulin Release ◽  
High Glucose ◽  
Second Phase ◽  
Dependent Manner ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Second Phases ◽  
High Concentrations ◽  
Dose Dependent ◽  
Stimulation Of

We have examined the effect of galanin infusion on glucose-stimulated release of insulin from the isolated perfused pancreas of the rat to better characterize the effect of galanin on the first and second phases of insulin release. The effects of galanin on insulin release stimulated by L-arginine or high concentrations of potassium were also examined. When perfusion of galanin was started 4 min before the start of perfusion of high glucose (16.7 mM), galanin (10(-8)-10(-11) M) inhibited both the first and second phases of insulin release in a dose-dependent manner. When perfusion of galanin (10(-8) or 10(-9) M) was started simultaneously with high glucose (16.7 mM), only the second phase of insulin release was suppressed (P less than 0.05). Galanin (10(-9) M) failed to inhibit insulin release stimulated by L-arginine (10 and 5 mM) or potassium (25 and 20 mM). These findings suggest that the inhibitory action of galanin on glucose-stimulated insulin release is exerted on early intracellular events that occur during the stimulation of insulin release and that are common to both phases. Because galanin does not inhibit insulin release stimulated by L-arginine or potassium, galanin may inhibit glucose-stimulated closure of potassium channels.

scholarly journals Abnormal glucose metabolism accompanies failure of glucose to stimulate insulin release from a rat pancreatic cell line (RINm5F)

1983 ◽  
Vol 212 (2) ◽  
pp. 439-443 ◽  
Author(s):  
P A Halban ◽  
G A Praz ◽  
C B Wollheim
Keyword(s):  
Glucose Metabolism ◽  
Cell Line ◽  
Insulin Release ◽  
Glucose Utilization ◽  
Rinm5f Cells ◽  
Pancreatic Cell ◽  
Abnormal Glucose Metabolism ◽  
Isolated Rat Islets ◽  
Stimulate Insulin Release ◽  
Stimulation Of

Glucose metabolism and insulin release were studied in isolated rat islets and in an insulin-producing rat cell-line (RINm5F). Intact islets displayed two components of glucose utilization, with glucose stimulation of insulin release being associated with the high-Km component (reflecting glucokinase-like activity). Glucose failed to stimulate insulin release from RINm5F cells, which only displayed a single low-Km component of glucose utilization. Only low-Km (hexokinase-like) glucose-phosphorylating activity was found for disrupted RINm5F cells. These changes in glucose metabolism may contribute towards the failure of glucose to stimulate insulin release from RINm5F cells.

Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets

1990 ◽  
Vol 259 (4) ◽  
pp. E548-E554 ◽  
Author(s):  
M. J. MacDonald ◽  
L. A. Fahien ◽  
D. I. McKenzie ◽  
S. M. Moran
Keyword(s):  
Tissue Culture ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Metabolic Pathways ◽  
Time Course ◽  
Reciprocal Relationship ◽  
Insulin Secretagogues ◽  
Low Glucose ◽  
Islet Survival ◽  
Stimulate Insulin Release

Agents that stimulate insulin release from fresh pancreatic islets were tested for their ability to capacitate pancreatic islets to secrete insulin and to support beta-cell survival in tissue culture. Capacitation was defined as the ability to release insulin after 24 h in culture in the presence of an insulinotropic concentration of a secretagogue. Viable islets that lose glucose-induced insulin release gradually regain it during culture for 24 h in 20 mM glucose. Survival was defined as the ability to regain glucose-induced insulin release. To measure insulin release after culture, islets were incubated with various secretagogues in Krebs-Ringer buffer for 1 h. Examples of the diverse patterns of responses included the following. Glucose was the only secretagogue that capacitated glucose-induced release. Leucine-, leucine plus glutamine-, and glyceraldehyde-induced release remained capacitated after culture with no secretagogue. Culture at high glucose completely inhibited leucine-induced release. Culture at low glucose (1 mM) or at both high leucine and glutamine abolished glucose-induced release. Only leucine and glutamine capacitated monomethyl succinate-induced release. All agents including subinsulinotropic glucose (1 mM), except D-glyceraldehyde, permitted islet survival. Thus the metabolic pathways for initiation, capacitation, and survival are not identical between and within secretagogues. There is a reciprocal relationship between leucine and glucose with respect to capacitation. Capacitation follows a time course, which suggests that it is regulated by enzyme induction.

Respiratory, ionic, and functional effects of succinate esters in pancreatic islets

1993 ◽  
Vol 264 (3) ◽  
pp. E428-E433 ◽  
Author(s):  
W. J. Malaisse ◽  
J. Rasschaert ◽  
M. L. Villanueva-Penacarrillo ◽  
I. Valverde
Keyword(s):  
Succinic Acid ◽  
Insulin Release ◽  
Methyl Esters ◽  
O2 Uptake ◽  
Biosynthetic Activity ◽  
Insulin Secretagogues ◽  
Net Uptake ◽  
Characteristic Features ◽  
45Ca Efflux ◽  
Stimulation Of

The methyl esters of succinic acid were introduced a few years ago as new potent insulin secretagogues. In the present study, they were found to increase O2 uptake by rat islets incubated in the absence or presence of D-glucose; to decrease 86Rb outflow from prelabeled islets; to stimulate biosynthetic activity in the islets, with a preferential effect on the synthesis of proinsulin; to inhibit 45Ca efflux from prelabeled islets perifused in the absence of extracellular Ca2+ but to augment 45Ca net uptake and to cause a biphasic stimulation of 45Ca outflow in islets incubated or perifused in the presence of extracellular Ca2+; and to evoke a biphasic stimulation of insulin release. The insulinotropic action of these methyl esters coincided with a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration, was concentration related in the 2-10 mM range, failed to be duplicated by succinic acid, displayed both Ca2+ dependency and resistance to a lowering of extracellular pH, and was operative in the absence of D-glucose whether or not the islets were stimulated by non-nutrient secretagogues. It is concluded that the respiratory, cationic, biosynthetic, and secretory responses of the islets to succinate methyl esters display the characteristic features usually encountered in the process of nutrient-stimulated insulin release.

Hyposmotic shock stimulates insulin secretion by two distinct mechanisms. Studies with the βHC9 cell

2002 ◽  
Vol 282 (5) ◽  
pp. E1070-E1076 ◽  
Author(s):  
Susanne G. Straub ◽  
Samira Daniel ◽  
Geoffrey W. G. Sharp
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Channel Blocker ◽  
Similar Data ◽  
Hypotonic Shock ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Chloride Channel Blocker ◽  
Hyposmotic Shock ◽  
Stimulation Of

Exposure of βHC9 cells to a Krebs-Ringer bicarbonate-HEPES buffer (KRBH) made hypotonic by a reduction of 25 mM NaCl resulted in a prompt stimulation of insulin release. The stimulation was transient, and release rates returned to basal levels after 10 min. The response resembles that of the first phase of glucose-stimulated insulin release. The response did not occur if the reduction in NaCl was compensated for by the addition of an equivalent osmolar amount of sorbitol, so the stimulation of release was due to the osmolarity change and not the reduction in NaCl. The hyposmotic shock released insulin in KRBH with or without Ca2+. The L-type Ca2+ channel blocker nitrendipine inhibited the response in normal KRBH but had no effect in KRBH without Ca2+ despite the latter response being larger than in the presence of extracellular Ca2+. Similar data were obtained with calciseptine, which also blocks L-type channels. The T-type Ca2+ channel blocker flunarizine was without effect, as was the chloride channel blocker DIDS. In parallel studies, the readily releasable pool of insulin-containing granules was monitored. Immunoprecipitation of the target-SNARE protein syntaxin and co-immunoprecipitation of the vesicle-SNARE VAMP-2 was used as an indicator of the readily releasable granule pool. After hypotonic shock in the presence of extracellular Ca2+, the amount of VAMP-2 coimmunoprecipitated by antibodies against syntaxin was much reduced compared with controls. Therefore, under these conditions, hypotonic shock stimulates exocytosis of the readily releasable pool of insulin-containing granules. No such reduction was seen in the absence of extracellular Ca2+. In conclusion, after reexamination of the effect of hyposmotic shock on insulin secretion in the presence and absence of Ca2+ (with EGTA in the medium), it is clear that two different mechanisms are operative under these conditions. Moreover, these two mechanisms may be associated with the release of two distinct pools of insulin-containing granules.

scholarly journals The stimulus-secretion coupling of glucose-induced insulin release. Insulin release due to glycogenolysis in glucose-deprived islets

1977 ◽  
Vol 164 (2) ◽  
pp. 447-454 ◽  
Author(s):  
W J Malaisse ◽  
A Sener ◽  
M Koser ◽  
M Ravazzola ◽  
F Malaisse-Lagae
Keyword(s):  
Insulin Release ◽  
Glucose Concentration ◽  
Essential Feature ◽  
Free Medium ◽  
Exogenous Glucose ◽  
Extracellular Glucose ◽  
Net Uptake ◽  
Low Glucose ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

1. When pancreatic islets are preincubated for 20h in the presence of glucose (83.3mM) and thereafter transferred to a glucose-free medium, theophylline (1.4mM) provokes a dramatic stimulation of insulin release. This phenomenon does not occur when the islets are preincubated for either 20h at low glucose concentration (5.6mM) or only 30 min at the high glucose concentration (83.3mM). 2. The insulinotropic action of theophylline cannot be attributed to contamination of the islets with exogenous glucose and is not suppressed by mannoheptulose. 3. The secretory response to theophylline is an immediate phenomenon, but disappears after 60min of exposure to the drug. 4. The release of insulin evoked by theophylline is abolished in calcium-depleted media containing EGTA. Theophylline enhances the net uptake of 45Ca by the islets. 5. Glycogen accumulates in the islets during the preincubation period, as judged by both ultrastructural and biochemical criteria. Theophylline significantly increases the rate of glycogenolysis during the final incubation in the glucose-free medium. 6. The theophylline-induced increase in glycogenolysis coincides with a higher rate of both lactate output and oxidation of endogenous 14C-labelled substrates. 7. These data suggest that stimulation of glycolysis from endogenous stores of glycogen is sufficient to provoke insulin release even in glucose-deprived islets, as if the binding of extracellular glucose to hypothetical plasma-membrane glucoreceptors is not an essential feature of the stimulus-secretion coupling process.

scholarly journals The biphasic stimulation of insulin secretion by bombesin involves both cytosolic free calcium and protein kinase C

1988 ◽  
Vol 253 (1) ◽  
pp. 193-202 ◽  
Author(s):  
S L Swope ◽  
A Schonbrunn
Keyword(s):  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Insulin Release ◽  
Secretory Response ◽  
Pancreatic Cell ◽  
Secretory Rate ◽  
Kinase C ◽  
Stimulate Insulin Release ◽  
Stimulation Of

Members of the bombesin family of peptides potently stimulate insulin release by HIT-T15 cells, a clonal pancreatic cell line. The response to bombesin consists of a large burst in secretion during the first 30 s, followed by a smaller elevation of the secretory rate, which persists for 90 min. The aim of this study was to identify the intracellular messengers involved in this biphasic secretory response. Addition of 100 nM-bombesin to cells for 20 s increased the cellular accumulation of [3H]diacylglycerol (DAG) by 40% and that of [3H]inositol monophosphate (InsP), bisphosphate (InsP2) and trisphosphate (InsP3) by 40%, 300%, and 800%, respectively. In contrast, cyclic AMP concentrations were unaffected. Bombesin stimulation of [3H]InsP3 formation was detected at 2 s, before the secretory response, which was not measurable until 5 s. Furthermore, the potency of bombesin to stimulate [3H]InsP3 generation (ED50 = 14 +/- 9 nM) agreed with its potency to stimulate insulin release (ED50 = 6 +/- 2 nM). Consistent with its effects on [3H]InsP3 formation, bombesin raised the intracellular free Ca2+ concentration [(Ca2+]i) from a basal value of 0.28 +/- 0.01 microM to a peak of 1.3 +/- 0.1 microM by 20 s. Chelation of extracellular Ca2+ did not abolish either the secretory response to bombesin or the rise in [Ca2+]i, showing that Ca2+ influx was not required. Although the Ca2+ ionophore ionomycin (100 nM) mimicked the [Ca2+]i response to bombesin, it did not stimulate secretion. However, pretreating cells with ionomycin decreased the effects of bombesin on both [Ca2+]i and insulin release, suggesting that elevation of [Ca2+]i was instrumental in the secretory response to this peptide. To determine the role of the DAG produced upon bombesin stimulation, we examined the effects of another activator of protein kinase C, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA did not affect [Ca2+]i, but it increased insulin secretion after a 2 min lag. However, an immediate increase in secretion was observed when ionomycin was added simultaneously with TPA. These data indicate that the initial secretory burst induced by bombesin results from the synergistic action of the high [Ca2+]i produced by InsP3 and DAG-activated protein kinase C. However, activation of protein kinase C alone appears to be sufficient for a sustained secretory response.

scholarly journals A single mechanism for the stimulation of insulin release and 86Rb+ efflux from rat islets by cationic amino acids

1982 ◽  
Vol 208 (2) ◽  
pp. 301-308 ◽  
Author(s):  
Stanislas Charles ◽  
Tatsuo Tamagawa ◽  
Jean-Claude Henquin
Keyword(s):  
Amino Acids ◽  
B Cells ◽  
Insulin Release ◽  
Cell Function ◽  
Dependent Manner ◽  
Free Medium ◽  
Rat Islets ◽  
Related Substances ◽  
Cationic Amino Acids ◽  
Stimulation Of

The mechanisms by which cationic amino acids influence pancreatic B-cell function have been studied by monitoring simultaneously 86Rb+ efflux and insulin release from perifused rat islets. The effects of two reference amino acids arginine and lysine were compared with those of closely related substances to define the structural requirements for recognition of these molecules as secretagogues. Arginine accelerated 86Rb+ efflux and increased insulin release in the absence or in the presence of 7mm-glucose. Its effects on efflux did not require the presence of extracellular Ca2+ or Na+, but its insulinotropic effects were suppressed in a Ca2+-free medium and inhibited in an Na+-free medium. Among arginine derivatives, only 2-amino-3-guanidinopropionic acid mimicked its effects on 86Rb+ efflux and insulin release; citrulline, guanidinoacetic acid, 3-guanidinopropionic acid and guanidine were inactive. Norvaline and valine also increased 86Rb+ efflux, but their effect required the presence of extracellular Na+; they did not stimulate insulin release. Lysine as well as the shorter-chain cationic amino acids ornithine and 2,4-diaminobutyric acid accelerated 86Rb+ efflux in a Ca2+- and Na+-independent manner. Their stimulation of insulin release was suppressed by Ca2+ omission, but only partially inhibited in an Na+-free medium. The uncharged glutamine and norleucine increased the rate of 86Rb+ efflux in the presence of glucose, only if extracellular Na+ was present. Norleucine slightly increased release in a Ca2+- and Na+-dependent manner. The effects of lysine on efflux and release were not mimicked by other related substances such as 1,5-diaminopentane and 6-aminohexanoic acid. The results suggest that the depolarizing effect of cationic amino acids is due to accumulation of these positively charged molecules in B-cells. This causes acceleration of the efflux of K+ (86Rb+) and activation of the influx of Ca2+ (which triggers insulin release). The prerequisite for the stimulation of B-cells by this mechanism appears to be the presence of a positive charge on the side chain of the amino acid, rather than a specific group.

STIMULATION OF INSULIN RELEASE BY MAITOTOXIN, AN ACTIVATOR OF VOLTAGE-DEPENDENT CALCIUM CHANNELS

1986 ◽  
Vol 7 (2) ◽  
pp. 107-112 ◽  
Author(s):  
ICHIRO NIKI ◽  
TATSUO TAMAGAWA ◽  
HATSUMI NIKI ◽  
ATSUSHI NIKI ◽  
TADATAKA KOIDE ◽  
...  
Keyword(s):  
Insulin Release ◽  
Voltage Dependent ◽  
Stimulation Of
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