Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon

Yamada, Satoko; Komatsu, Mitsuhisa; Aizawa, Toru; Sato, Yoshihiko; Yajima, Hiroki; Yada, T.; Hashiguchi, Suzuko; Yamauchi, Kazuyo; Hashizume, Kiyoshi

doi:10.1677/joe.0.1720345

Cited by 12 publications

(13 citation statements)

References 44 publications

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“…2A, left panel) (9)(10)(11)(12). Glucose at concentrations higher than 5.5 mm caused TDP in a concentration-dependent manner as previously described (11,12,17), which was significantly augmented by forskolin ( Fig. 2A, left panel).…”

Section: Effects Of Forskolin On Nutrient-induced Time-dependent Potesupporting

confidence: 78%

“…We previously reported that cerulenin, which inhibits protein acylation at a concentration of 30 -100 g/ml, specifically inhibits nutrient-induced insulin release and glucoseinduced TDP (12,22). We therefore examined whether protein acylation was involved in the enhancement of nutrient-induced TDP by forskolin.…”

Section: Effects Of Nan 3 and Cerulenin On Forskolin Enhancement Of Tdpmentioning

confidence: 98%

“…Insulin release was measured in static incubation experiments as previously reported (12). In brief, five size-matched islets were first incubated for 60 min in KRB buffer containing the indicated concentrations of test substances at 37 C (preincubation).…”

Section: Measurement Of Insulin Releasementioning

confidence: 99%

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Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

et al. 2002

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Isolated rat islets were exposed to cAMP-elevating agents and/or nutrients. Insulin exocytosis subsequently triggered by a depolarizing concentration of K(+) or a stimulatory concentration of glucose was employed as an index of time-dependent potentiation (TDP). Stimulatory concentrations (>or=5.5 mM) of glucose caused TDP, and 6 micro M forskolin (an activator of adenylyl cyclase) significantly enhanced it (3.1-fold at most). Forskolin produced an 8.0-fold increase in islet cell cAMP; however, it returned to the baseline after washout by the time of stimulation of exocytosis. Two millimoles of dibutyryl cAMP (a cAMP analog), 0.1 mM isobutylmethylxanthine (a phosphodiesterase inhibitor), and 100 nM glucagon-like peptide-1 (an incretin hormone) also enhanced glucoseinduced TDP. The time-dependent effect of cAMP was not attenuated by protein kinase A inhibitors (200 micro M adenosine 3',5'-cyclic monophosphothioate, Rp isomer, and 10 micro M H89). Although glucose-induced TDP was attenuated by NaN(3) (a mitochondrial poison) and cerulenin (an inhibitor of protein acylation), cAMP enhancement of it was unaffected by these agents. In conclusion, cAMP time-dependently stimulates insulin exocytosis, provided the extracellular glucose concentration is equivalent to or higher than ambient plasma levels. Protein kinase A, mitochondrial metabolism, and protein acylation are not involved in this cAMP action. Incretin stimulation of insulin exocytosis may occur in part via this mechanism.

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Section: Effects Of Forskolin On Nutrient-induced Time-dependent Potesupporting

confidence: 78%

Section: Effects Of Nan 3 and Cerulenin On Forskolin Enhancement Of Tdpmentioning

confidence: 98%

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Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

et al. 2002

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“…By mediating protein-membrane and protein-protein interactions, protein acylation is thought to be important for cell signaling, e.g., in the T cell (25,26,34,39) and ␤-cell (6,31,41,44). We found that inhibitors of protein acylation blocked the distal inhibitory effects of NE, somatostatin, galanin, and PGE 2 .…”

mentioning

confidence: 75%

Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE₂

Cheng

Straub

Sharp

2003

American Journal of Physiology-Endocrinology and Metabolism

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The major physiological inhibitors of insulin secretion, norepinephrine, somatostatin, galanin, and prostaglandin E 2, act via specific receptors that activate pertussis toxin (PTX)-sensitive G proteins. Four inhibitory mechanisms are known: 1) activation of ATP-sensitive K channels and repolarization of the ␤-cell; 2) inhibition of L-type Ca 2ϩ channels; 3) decreased activity of adenylyl cyclase; and 4) inhibition of exocytosis at a "distal" site in stimulus-secretion coupling. We have examined the underlying mechanisms of inhibition at this distal site. In rat pancreatic islets, 2-bromopalmitate, cerulenin, and polyunsaturated fatty acids, all of which suppress protein acyltransferase activity, blocked the distal inhibitory effects of norepinephrine in a concentration-dependent manner. In contrast, control compounds such as palmitate, 16-hydroxypalmitate, and etomoxir, which do not block protein acylation, had no effect. Furthermore, 2-bromopalmitate also blocked the distal inhibitory actions of somatostatin, galanin, and prostaglandin E 2. Importantly, neither 2-bromopalmitate nor cerulenin affected the action of norepinephrine to decrease cAMP production. We also examined the effects of norepinephrine, 2-bromopalmitate, and cerulenin on palmitate metabolism. Palmitate oxidation and its incorporation into lipids seemed not to contribute to the effects of 2-bromopalmitate and cerulenin on norepinephrine action. These data suggest that protein acylation mediates the distal inhibitory effect on insulin secretion. We propose that the inhibitors of insulin secretion, acting via PTX-sensitive G proteins, activate a specific protein acyltransferase, causing the acylation of a protein or proteins critical to exocytosis. This particular acylation and subsequent disruption of the essential and precise interactions involved in core complex formation would block exocytosis. rat pancreatic islets; ␤-cell; signaling; pertussis toxin; G proteins INSULIN SECRETION is a complex process regulated by nutrients, such as glucose and amino acids, and hormonal and neural factors that provide stimulatory and inhibitory influences on the pancreatic ␤-cells. The major physiological inhibitors, such as norepinephrine (NE), somatostatin, prostaglandin E 2 (PGE 2 ), and galanin, can inhibit insulin secretion that is stimulated by all of the nutrient and modulatory pathways. They interact with specific G protein-linked receptors at the plasma membrane, which activate pertussis toxin (PTX)-sensitive G i and G o proteins that mediate the inhibition of insulin secretion (17,27,30).The inhibitory pathways act in contradictory fashion on many of the same sites as the stimulatory pathways (30). For example, 1) inhibitors activate the ATP-sensitive K (K ATP ) channel, repolarize or hyperpolarize the cell membrane, and thus inhibit the action of glucose that depolarizes the membrane via closure of this channel; 2) inhibitors decrease the activity of the Ltype Ca 2ϩ channel by two means, indirectly by the activation of the K ATP channel and hyperp...

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“…The b-cell priming by glucose occurs in a K ATP channelindependent manner, because the potentiation was totally resistant to a high concentration of diazoxide, an opener of K ATP channels 12 . Furthermore, TDP occurs under stringent Ca 2+ -free conditions and therefore [Ca 2+ ] i elevation is not required 27 . Taken together, these observations suggest that the second phase observed under a square wave high-glucose application is the triggered insulin release followed by enhancement by TDP.…”

Section: Priming Of B-cellsmentioning

confidence: 99%

Glucose‐stimulated insulin secretion: A newer perspective

Komatsu

Takei

Ishii

et al. 2013

J of Diabetes Invest

214

166

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Existing concepts and models for glucose-stimulated insulin secretion (GSIS) are overviewed and a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model has been created on the basis of in vitro data on application of a square wave high glucose in the absence of any other stimulatory inputs. Glucose elicits rapid insulin release through an adenosine triphosphate-sensitive K + channel (K ATP channel)-dependent mechanism, which is gradually augmented in a K ATP channel-independent manner. Biphasic GSIS thus occurs. In the body, the b-cells are constantly exposed to stimulatory signals, such as glucagon-like peptide 1 (GLP-1), parasympathetic inputs, free fatty acid (FFA), amino acids and slightly suprathreshold levels of glucose, even at fasting. GLP-1 increases cellular cyclic adenosine monophosphate, parasympathetic stimulation activates protein kinase C, and FFA, amino acids and glucose generate metabolic amplification factors. Plasma glucose concentration gradually rises postprandially under such tonic stimulation. We hypothesize that these stimulatory inputs together make the b-cells responsive to glucose independently from its action on K ATP channels. Robust GSIS in patients with a loss of function mutation of the sulfonylurea receptor, a subunit of K ATP channels, is compatible with this hypothesis. Furthermore, pre-exposure of the islets to an activator of protein kinase A and/or C makes b-cells responsive to glucose in a K ATP channel-and Ca 2+-independent manner. We hypothesize that GSIS occurs in islet b-cells without glucose regulation of K ATP channels in vivo, for which priming with cyclic adenosine monophosphate, protein kinase C and non-glucose nutrients are required. To understand the physiology of GSIS, comprehensive integration of accumulated knowledge is required. (J Diabetes Invest,

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Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon

Abstract: When isolated rat pancreatic islets are treated with 16·7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 50 mM KCl ]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.

Cited by 12 publications

References 44 publications

Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE₂

Glucose‐stimulated insulin secretion: A newer perspective

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Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon

Cited by 12 publications

References 44 publications

Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Time-Dependent Stimulation of Insulin Exocytosis by 3′,5′-Cyclic Adenosine Monophosphate in the Rat Islet β-Cell

Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE2

Glucose‐stimulated insulin secretion: A newer perspective

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Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE₂