Insulinotropic action of α-d-glucose pentaacetate: functional aspects

1997 ◽  
Vol 273 (6) ◽  
pp. E1090-E1101
Author(s):  
Willy J. Malaisse ◽  
Carmen Sánchez-Soto ◽  
M. Elena Larrieta ◽  
Marcia Hiriart ◽  
Hassan Jijakli ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Insulin Release ◽  
Methyl Acetate ◽  
Cytochalasin B ◽  
Secretory Response ◽  
Coupling Mechanism ◽  
Functional Aspects ◽  
Acetate Methyl ◽  
Glucose Pentaacetate ◽  
Stimulate Insulin Release

The functional determinants of the insulinotropic action of α-d-glucose pentaacetate were investigated in rat pancreatic islets. The ester mimicked the effect of nutrient secretagogues by recruiting individual B cells into an active secretory state, stimulating proinsulin biosynthesis, inhibiting86Rb outflow, and augmenting45Ca efflux from prelabeled islets. The secretory response to the ester was suppressed in the absence of Ca2+ and potentiated by theophylline or cytochalasin B. The generation of acetate from the ester apparently played a small role in its insulinotropic action. Thus acetate, methyl acetate, ethyl acetate, α-d-galactose pentaacetate, and β-d-galactose pentaacetate all failed to stimulate insulin release. The secretory response to α-d-glucose pentaacetate was reproduced by β-d-glucose pentaacetate and, to a lesser extent, by β-l-glucose pentaacetate. It differed from that evoked by unesterifiedd-glucose by its resistance to 3- O-methyl-d-glucose,d-mannoheptulose, and 2-deoxy-d-glucose. It is concluded that the insulinotropic action of α-d-glucose pentaacetate, although linked to the generation of the hexose from its ester, entails a coupling mechanism that is not identical to that currently implied in the process of glucose-induced insulin release.

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.

THE EFFECT OF FASTING AND SELECTIVE RE-FEEDING ON INSULIN RELEASE IN THE RAT

1973 ◽  
Vol 72 (1) ◽  
pp. 46-53 ◽  
Author(s):  
D. S. Turner ◽  
D. A. B. Young
Keyword(s):  
Insulin Release ◽  
Acute Effect ◽  
Secretory Response ◽  
Release Mechanism ◽  
Β Cell ◽  
Intestinal Hormones ◽  
Intravenous Glucose ◽  
Glucose Ingestion ◽  
Glucose Test ◽  
Insulin Secretory Response

ABSTRACT The insulin secretory response in the rat to intravenous glucose was found to be greatly impaired by fasting for three days, whereas that to orally administered glucose was not significantly affected. Rats fasted for two days were given either protein or starch pellets for six hours, and then fasted for a further eighteen hours before the intravenous glucose test. The protein pre-feeding failed to affect significantly the subsequent insulin secretory response to intravenous glucose, whereas starch prefeeding greatly enhanced it. It is suggested that intestinal hormones released by glucose ingestion may exert not only an acute effect on insulin release, but also a 'priming' effect on the insulin release mechanism of the β cell, which enables it to respond to the subsequent stimulus of glucose alone.

The Flavor Property of Soft Cheese Fermented by Two Stains of Streptococcus thermophilus and Made of Reconstituted Milk

2011 ◽  
Vol 396-398 ◽  
pp. 1536-1540
Author(s):  
Yan Hua Li ◽  
Lan Wei Zhang ◽  
Wei Jun Wang ◽  
Li Li Zhang ◽  
Xue Han ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Butyl Acetate ◽  
Streptococcus Thermophilus ◽  
Acetate Methyl ◽  
Soft Cheese ◽  
Significant Difference ◽  
Cheese Volatiles ◽  
Methyl Butyrate ◽  
Reconstituted Milk ◽  
The Impact

The effect of reconstituted milk inoculation with Streptococcus thermophilus TM11 and Streptococcus thermophilus SP 1.1 on soft cheese volatiles was investigated. The impact flavors of 2,3-butanedione, 2,3-pentanedione, ethyl acetate, methyl butyrate, ethyl butyrate, butyl acetate and butyric acid were only detected in the fermented cheeses. Levels of diketones were higher in the cheeses fermented by mixed cultures than single culture, while levels of esters except ethyl acetate and butyl acetate showed an opposite tendency. There was significant difference in the levels of 2-hexenal and 2-nonenal among the cheeses. Other compounds originated from lipid oxidation, Strecker degradation, biosynthesis and forages were not significantly influenced by milk inoculation with Streptococcus thermophilus.

Effects of l-leucine, its 2-keto acid metabolite and its nonmetabolized analogue on rat tumoral islet cell function

1988 ◽  
Vol 1 (1) ◽  
pp. 69-76 ◽  
Author(s):  
V. Leclercq-Meyer ◽  
J. Marchand ◽  
A. Sener ◽  
F. Blachier ◽  
W. J. Malaisse
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Islet Cells ◽  
Adenine Nucleotides ◽  
Secretory Response ◽  
Acid Metabolite ◽  
Dual Effect ◽  
Islet Cell Function ◽  
Insulinoma Cells ◽  
Stimulation Of

ABSTRACT l-Leucine and 2-ketoisocaproate stimulated insulin release from perifused rat tumoral islet cells (RINm5F line). The secretory response coincided with an increase in the intracellular ATP/ADP ratio, a stimulation of 45Ca outflow from cells perifused in the presence of extracellular Ca2+, and an increase in 32P efflux from cells prelabelled with radioactive orthophosphate. In contrast to d-glucose, however, l-leucine or 2-ketoisocaproate failed to decrease 86Rb outflow, to inhibit 45Ca outflow from cells perifused in the absence of Ca2+ and to enhance the labelling of inositol-containing phospholipids in cells exposed to myo-[2-3H]inositol. These findings suggest that d-glucose, l-leucine and 2-ketoisocaproate exert dissimilar effects on the subcellular distribution of adenine nucleotides and/or 86Rb. The nonmetabolized analogue of l-leucine, 2-aminobicyclo-[2.2.1]heptane-2-carboxylic acid (BCH), also caused an initial stimulation of insulin release and 32P efflux, but this was soon followed by a severe and irreversible inhibition of insulin output, associated with a permanent enhancement of 86Rb outflow. The dual ionic and secretory response to BCH is interpreted in the light of its dual effect on the catabolism of endogenous amino and fatty acids, and raises the view that BCH could be used to interfere with the function of insulinoma cells.

scholarly journals The stimulus–secretion coupling 4-methyl-2-oxopentanoate-induced insulin release

1979 ◽  
Vol 184 (2) ◽  
pp. 303-311 ◽  
Author(s):  
J C Hutton ◽  
A Sener ◽  
W J Malaisse
Keyword(s):  
Insulin Release ◽  
Metabolic Flux ◽  
Energy Charge ◽  
Hyperbolic Function ◽  
Maximal Response ◽  
Coupling Mechanism ◽  
Adenylate Energy Charge ◽  
Atp Content ◽  
45Ca Uptake ◽  
Stimulus Secretion Coupling

1. Pancreatic islet insulin secretion and 45Ca uptake showed similar responses to variation in the extracellular concentration of 4-methyl-2-oxopentanoate with a threshold at 4 mM and a maximal response at a 25 mM concentration. 2. Islet respiration, acetoacetate production and rates of substrate utilization, oxidation and amination all changed as a simple hyperbolic function of 4-methyl-2-oxopentanoate concentration and exhibited a maximal response at 25 mM. 3. The responses of ATP content, [ATP]/[ADP] ratio, adenylate energy charge and [NADH]/[NAD+] ratio were also hyperbolic in nature but were maximally elevated at lower concentrations of the secretagogue. The islet [NADPH]/[NADP+] ratio, however, was tightly correlated with parameters of metabolic flux, 45Ca uptake and insulin release. 4. NH4+ and menadione, agents that promote a more oxidized state in islet NADP, did not affect islet ATP content or the rates of [U-14C]4-methyl-2-oxopentanoate oxidation or amination, but markedly inhibited islet 45Ca uptake and insulin release. 5. It is proposed that changes in the redox state of NADP and Ca transport may serve as mediators in the stimulus-secretion coupling mechanism of insulin release induced by 4-methyl-2-oxopentanoate.

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