Sulfonylureas can Stimulate Insulin Release by Flip-Flop across Phospholipid Membranes

2016 ◽  
Vol 06 (01) ◽  
Author(s):  
Jamal Alruwaili
Keyword(s):  
Insulin Release ◽  
Phospholipid Membranes ◽  
Flip Flop ◽  
Stimulate Insulin Release

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.

P2 Receptor Agonists Stimulate Insulin Release from Human Pancreatic Islets

Pancreas ◽  
2001 ◽  
Vol 22 (1) ◽  
pp. 69-71 ◽  
Author(s):  
Josepha Fernandez-Alvarez ◽  
Dominique Hillaire-Buys ◽  
Marie-Madeleine Loubati??res-Mariani ◽  
Ramon Gomis ◽  
Pierre Petit
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
P2 Receptor ◽  
Human Pancreatic Islets ◽  
Receptor Agonists ◽  
Stimulate Insulin Release

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.

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.

scholarly journals Human Anti-CD38 Autoantibodies Raise Intracellular Calcium and Stimulate Insulin Release in Human Pancreatic Islets

Diabetes ◽  
2001 ◽  
Vol 50 (5) ◽  
pp. 985-991 ◽  
Author(s):  
A. Antonelli ◽  
G. Baj ◽  
P. Marchetti ◽  
P. Fallahi ◽  
N. Surico ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Human Pancreatic Islets ◽  
Stimulate Insulin Release

Insulinotropic action of glutamic acid dimethyl ester

1994 ◽  
Vol 267 (4) ◽  
pp. E573-E584 ◽  
Author(s):  
A. Sener ◽  
I. Conget ◽  
J. Rasschaert ◽  
V. Leclercq-Meyer ◽  
M. L. Villanueva-Penacarrillo ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Insulin Release ◽  
Dimethyl Ester ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
O2 Uptake ◽  
Acid Dimethyl Ester ◽  
Insulin Dependent ◽  
Early Fall ◽  
Stimulate Insulin Release

Glutamic acid dimethyl ester (GME; 3.0–10.0 mM) enhanced insulin release evoked by 6.0–8.3 mM D-glucose, 1.0–10.0 mM L-leucine, or 5.0–10.0 mM 2-amino-bicyclo(2,2,1)heptane-2-carboxylic acid, causing a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration. In the absence of D-glucose, GME also unmasked the insulinotropic potential of glibenclamide. In islets exposed to L-leucine, the insulinotropic action of GME coincided with an early fall and later increase in 86Rb outflow and augmentation of 45Ca outflow from prelabeled islets. The measurement of O2 uptake, NH4+ output, production of 14CO2 from islets prelabeled with [U-14C]palmitate, generation of 14C-labeled amino acids and 14CO2 from the dimethyl ester of either L-[1-14C]glutamic acid or L-[U-14C]glutamic acid, and D-[2-14C]glucose as well as D-[6-14C]glucose oxidation in the presence or absence of GME indicated that the latter ester was efficiently converted to L-glutamate and its further metabolites. The overall gain in O2 uptake represented the balance between GME oxidation and its sparing action on the catabolism of endogenous fatty acids and exogenous D-glucose. It is proposed that GME might represent a new tool to bypass beta-cell defects in D-glucose transport, phosphorylation, and further metabolism and, hence, to stimulate insulin release in experiments conducted in animal models of non-insulin-dependent diabetes mellitus.

scholarly journals Interrelationship of islet metabolism, adenosine triphosphate content and insulin release

1973 ◽  
Vol 132 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Stephen J. H. Ashcroft ◽  
L. Chatra C. Weerasinghe ◽  
Philip J. Randle
Keyword(s):  
Insulin Release ◽  
Close Association ◽  
Metabolic Inhibitors ◽  
Atp Content ◽  
Exogenous Substrate ◽  
Islet Metabolism ◽  
Mouse Pancreatic Islets ◽  
Oxidation Of Glucose ◽  
Stimulate Insulin Release ◽  
Exogenous Substrates

The oxidation of some exogenous substrates and their effects on ATP content and insulin release in mouse pancreatic islets were measured. The ATP concentration of islets incubated without exogenous substrate shows a gradual decrease, which can be prevented by glucose or mannose (20mm) or leucine (2.5mm); d-glyceraldehyde (5mm) is as effective as glucose (5mm); fructose or N-acetylglucosamine (20mm), pyruvate (10mm) and dl-3-hydroxybutyrate (2mm) are less effective; galactose (20mm), acetate (10mm), octanoate (2mm) and succinate (10mm) have no ATP-maintaining ability. Islets oxidize glucose, mannose, glyceraldehyde, leucine and, less readily, N-acetylglucosamine and glucosamine; galactose, however, is poorly metabolized. Mannoheptulose inhibits the oxidation of glucose but not of glyceraldehyde. Insulin release, measured over a 2h incubation, is stimulated by glucose, mannose, leucine, glyceraldehyde or glucosamine but not by fructose or N-acetylglucosamine. The latter, however, potentiates the effects of glucose or glyceraldehyde (5mm) or leucine (2.5mm) on release; the potentiating effects are inhibited by mannoheptulose, which also blocks glucose-, but not glyceraldehyde- or leucine-stimulated release. In the presence of glucose (20mm), metabolic inhibitors depress insulin release and islet ATP content in parallel. However, rates of insulin release and ATP content measured after incubation with various combinations of exogenous substrates do not appear to be correlated. Sulphonylureas stimulate insulin release but decrease islet ATP concentrations. These results provide further evidence of a close association between the metabolic activity of exogenous substrates and their ability to initiate insulin release. Glucoreceptor models are formulated in the light of these observations and discussed.

Effects of tetracaine on insulin release and calcium handling by rat pancreatic islets

1987 ◽  
Vol 252 (6) ◽  
pp. E727-E733
Author(s):  
S. M. el Motal ◽  
M. C. Pian-Smith ◽  
G. W. Sharp
Keyword(s):  
Tissue Culture ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Culture Conditions ◽  
Isolated Islets ◽  
Calcium Handling ◽  
Ca Channels ◽  
Rat Pancreatic Islets ◽  
Voltage Dependent ◽  
Stimulate Insulin Release

The effects of tetracaine on insulin release and 45Ca2+ handling by rat pancreatic islets have been studied under basal (2.8 mM glucose), glucose-stimulated (5.6, 8.3, and 16.7 mM glucose), and 3-isobutyl-1-methylxanthine (IBMX)-stimulated conditions. Islets were isolated by the use of collagenase and used either directly (freshly isolated islets) or after a period under tissue culture conditions. Tetracaine was found to stimulate insulin release under basal conditions, to inhibit glucose-stimulated insulin release, and to potentiate insulin release stimulated by IBMX. In studies on the mechanisms underlying these effects, tetracaine was found to decrease glucose-stimulated net retention of 45Ca2+ (by an action to block the voltage-dependent Ca channels) and to mobilize Ca2+ from intracellular stores. These two actions form the basis for the inhibition of glucose-stimulated insulin release, which depends heavily on Ca2+ entry via the voltage-dependent channels and the synergism with IBMX to potentiate release. No inhibition of IBMX-stimulated release occurs because IBMX does not use the voltage-dependent channels to raise intracellular Ca2+.

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