The stimulus-secretion coupling of amino acid-induced insulin release

Sener, Abdullah; Somers, Guido; Devis, Ghislain; Malaisse, Willy

doi:10.1007/bf00251281

Cited by 52 publications

(20 citation statements)

References 25 publications

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“…Insulin release was also augmented by the two other cationic amino acids, ornithine and 2,4-diaminobutyric acid; this increase had an absolute requirement for extracellular Ca2+, but was only partially inhibited in the absence of Na+ (Table 3). In agreement with the results of a recent study using incubated rat islets (Sener et al, 1981), glutamine was without effect and norleucine increased insulin release (Table 3). Interestingly, the effect of norleucine was much weaker than that of related cationic amino acids and was completely suppressed in the absence of Na+.…”

Section: Na+ and Ca2+supporting

confidence: 92%

“…The effect of guanidinoacetic acid could not be confirmed in vivo (Aynsley-Green & Alberti, 1974) or in vitro (Alberti & Whalley, 1973), but the cationic amino acids 2-amino-3-guanidinopropionic acid and 2amino-4-guanidinobutyric acid increased insulin release in the presence of glucose (Alberti & Whalley, 1973). In one report (Sener et al, 1981) norvaline was found to stimulate insulin release, but it proved inactive in this and two other studies (Alberti & Whalley, 1973;Sch6nborn et al, 1975). Taken together our results and those of Alberti & Whalley (1973) show that the insulinotropic property of arginine is lost if the ionization state of the molecule is altered by removing one of its basic groups.…”

Section: Na+ and Ca2+mentioning

confidence: 71%

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

Charles

Tamagawa

Henquin

1982

Biochemical Journal

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The mechanisms by which cationic amino acids influence pancreatic B-cell function have been studied by monitoring simultaneously (86)Rb(+) 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 (86)Rb(+) 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 Ca(2+) or Na(+), but its insulinotropic effects were suppressed in a Ca(2+)-free medium and inhibited in an Na(+)-free medium. Among arginine derivatives, only 2-amino-3-guanidinopropionic acid mimicked its effects on (86)Rb(+) efflux and insulin release; citrulline, guanidinoacetic acid, 3-guanidinopropionic acid and guanidine were inactive. Norvaline and valine also increased (86)Rb(+) 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 (86)Rb(+) efflux in a Ca(2+)- and Na(+)-independent manner. Their stimulation of insulin release was suppressed by Ca(2+) omission, but only partially inhibited in an Na(+)-free medium. The uncharged glutamine and norleucine increased the rate of (86)Rb(+) efflux in the presence of glucose, only if extracellular Na(+) was present. Norleucine slightly increased release in a Ca(2+)- 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(+) ((86)Rb(+)) and activation of the influx of Ca(2+) (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.

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Section: Na+ and Ca2+supporting

confidence: 92%

Section: Na+ and Ca2+mentioning

confidence: 71%

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

Charles

Tamagawa

Henquin

1982

Biochemical Journal

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“…Glutamine is known to potentiate the secretory effects of leucine in islet cells (Sener et al, 1981). Glutamine (10mM) alone had no significant effect on the rate of 45Ca2+ efflux, whatever the ionic composition of the medium.…”

Section: Effects Of Leucine On 4sca2+ Effluxmentioning

confidence: 88%

Distinct effects of various amino acids on 45Ca2+ fluxes in rat pancreatic islets

Charles¹,

Henquin²

1983

Biochemical Journal

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The effects of three types of amino acids on 45Ca2+ fluxes in rat pancreatic islets have been compared. Alanine, a non-insulinotropic neutral amino acid, transported with Na+, increased 45Ca2+ efflux in the presence or in the absence of extracellular Ca2+, but not in the absence of Na+. Its effects in Na+-solutions were practically abolished by 7 mM-glucose. Alanine slightly stimulated 45Ca2+ influx (5 min uptake) only when Na+ was present. Two insulinotropic cationic amino acids (arginine and lysine) triggered similar changes in 45Ca2+ efflux. They accelerated the efflux in the presence of Ca2+ and inhibited the efflux in a Ca2+-free medium, whether glucose was present or not. In an Na+-free Ca2+-medium, arginine and lysine markedly accelerated 45Ca2+ efflux, but this effect was suppressed by 7 mM-glucose. Arginine stimulated 45Ca2+ influx irrespective of the presence or absence of glucose and Na+. Leucine, a neutral insulinotropic amino acid well metabolized by islet cells, inhibited 45Ca2+ efflux from the islets in a Ca2+-free medium; this effect was potentiated by glutamine. In the presence of Ca2+ and Na+, leucine was ineffective alone, but triggered a marked increase in 45Ca2+ efflux when combined with glutamine. In an Na+-free Ca2+-medium, leucine accelerated 45Ca2+ efflux to the same extent with or without glutamine. Leucine also stimulated 45Ca2+ influx in the presence or in the absence of Na+, but its effects were potentiated by glutamine only in the presence of Na+. The results show that amino acids of various types cause distinct changes in 45Ca2+ fluxes in pancreatic islets. Certain of these changes involve an Na+-mediated mobilization of cellular Ca2+ from sequestering sites where glucose appears to exert an opposite effect.

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“…However, OCR, Ca 2+ and ISR were still robustly stimulated by glucose and, furthermore, insulin secretion was still observable in the presence of Ca 2+ channel blockade, indicating that the CMCP was still operational. In islets from control rats, blocking Ca 2+ influx by L-type Ca 2+ channels abolishes sustained insulin secretion by all known physiological secretagogues including glucose, fatty acids [27] and amino acids [28], as well as potentiators of nutrient-stimulated ISR including acetylcholine and GLP-1 [13]. Thus, the continued secretion of insulin in the presence of nimodipine observed in islets 3 weeks after the onset of hyperglycaemia was unexpected, as was the ability to secrete insulin in response to glucose by islets that do not decrease OCR in response to blocking Ca 2+ influx.…”

Section: Discussionmentioning

confidence: 99%

Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes

et al. 2013

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Aims/hypothesis Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca2+) influx and oxygen consumption rate (OCR) that is correlated with insulin secretion rate (ISR). To explain these observations, we have proposed a mechanism whereby the activation of a highly energetic process (Ca2+/metabolic coupling process [CMCP]) by Ca2+ mediates the stimulation of ISR. The aim of the study was to test whether impairment of the CMCP could play a role in the development of type 2 diabetes. Methods Glucose- and Ca2+-mediated changes in OCR and ISR in isolated islets were compared with the time course of changes of plasma insulin concentrations observed during the progression to hyperglycaemia in a rat model of type-2 diabetes (the University of California at Davis type 2 diabetes mellitus [UCD-T2DM] rat). Islets were isolated from UCD-T2DM rats before, 1 week, and 3 weeks after the onset of hyperglycaemia. Results Glucose stimulation of cytosolic Ca2+ and OCR was similar for islets harvested before and 1 week after the onset of hyperglycaemia. In contrast, a loss of decrement in islet OCR and ISR in response to Ca2+ channel blockade coincided with decreased fasting plasma insulin concentrations observed in rats 3 weeks after the onset of hyperglycaemia. Conclusions/interpretation These results suggest that phenotypic impairment of diabetic islets in the UCD-T2DM rat is downstream of Ca2+ influx and involves unregulated stimulation of the CMCP. The continuously elevated levels of CMCP induced by chronic hyperglycaemia in these islets may mediate the loss of islet function.

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The stimulus-secretion coupling of amino acid-induced insulin release

Cited by 52 publications

References 25 publications

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

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

Distinct effects of various amino acids on 45Ca2+ fluxes in rat pancreatic islets

Loss of coupling between calcium influx, energy consumption and insulin secretion associated with development of hyperglycaemia in the UCD-T2DM rat model of type 2 diabetes

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