Islets-Activating Protein (IAP) in Bordetella pertussis that Potentiates Insulin Secretory Responses of Rats

Yajima, Motoyuki; Hosoda, Koichi; Kanbayashi, Yoshinori; Nakamura, Tsutomu; Nogimori, Katsumi; Mizushima, Yutaka; Nakase, Yasukiyo; Ui, Michio

doi:10.1093/oxfordjournals.jbchem.a131904

Cited by 178 publications

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“…The novel factor produced by whooping cough bacteria was soon purified to homogeneity from the culture supernatant of B. pertussis by Ui and colleagues. 2,3) The purified factor was initially introduced under the name islet-activating protein and is now commonly known as PTX.…”

Section: Attenuation Of Epinephrine-induced Hy-perglycemia In Rats Prmentioning

confidence: 99%

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

Katada

2012

Biological & Pharmaceutical Bulletin

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Pertussis toxin (PTX) produced by Bordetella pertussis was first introduced by Ui and his colleagues in research on signal transduction under the name islet-activating protein in 1979, when the mechanism of toxin-induced stimulation of insulin release from pancreatic islets was reported in the rat. The stimulatory effect of PTX in vivo results from the blockage of α 2 -adrenergic receptor-mediated inhibition of insulin release. The receptor-induced inhibition of cAMP formation was also abolished in pancreatic islets isolated from PTX-treated rats, suggesting that the toxin caused uncoupling of adenylyl cyclase inhibition from receptor stimulation. The action of PTX on isolated membranes required a cytosolic factor, nicotinamide adenine dinucleotide (NAD), and the uncoupling induced by PTX was shown to be due to the toxin-catalyzed ADP-ribosylation of a 41-kDa protein with NAD as another substrate. The 41-kDa PTX substrate was soon identified and purified as the α-subunit of the inhibitory G protein that transmits an inhibitory signal from membrane receptors to adenylyl cyclase. After demonstration of the molecular mechanism of PTX, the toxin was widely utilized as a probe for identifying and analyzing major αβγ-trimeric G proteins. Thus, PTX-sensitive G proteins appeared to carry positive and negative signals from many membrane receptors to a variety of effectors other than adenylyl cyclase.

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Section: Attenuation Of Epinephrine-induced Hy-perglycemia In Rats Prmentioning

confidence: 99%

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

Katada

2012

Biological & Pharmaceutical Bulletin

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“…Strnad, Department of Pharmacology and Toxicology, Medical College of Virginia, Box 613 MCV Station, Richmond, VA 23298-0001, USA Pertussis toxin, produced by the bacterium Bordetella pertussis, first gained recognition for its ability to produce certain in vivo responses including sensitization to histamine [ 11, hypoglycemia [2], and a leukocytosis associated with elevated levels of circulating lymphocytes [3,4]. The toxin consists of six subunits [5], the largest (28 kDa) of which is a catalytic moiety (the A subunit), while the other five, ranging in molecular mass from 9.3 to 23 kDa, are associated to form a pentameric binding component (the B oligomer).…”

Section: Introductionmentioning

confidence: 99%

“…in certain cell systems, the B oligomer may play a more active role in the modulation of cellular functions has been provided by Tamura et al [lo] who found that the resolved B oligomer of pertussis toxin stimulated mitosis in murine splenocytes and enhanced glucose oxidation in rat adipocytes. Despite the important implications of these findings with respect to the lymphocytosis-promoting [3,4] and hypoglycemic [2] physiological effects of the toxin, the mechanism of action of B-oligomer-mediated responses has remained undefined.…”

Section: Introductionmentioning

confidence: 99%

Human T lymphocyte mitogenesis in response to the B oligomer of pertussis toxin is associated with an early elevation in cytosolic calcium concentrations

Strnad

Carchman

1987

FEBS Letters

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Pertussis toxin was found to serve as a mitogen in the human T lymphocyte, an effect which could be mimicked by its resolved binding component, the B oligomer. The mechanism of action of this component appeared to involve a rapid and sustained elevation of cytosolic calcium levels, as monitored by fura-fluorescence. The source of mobilized calcium was predominantly extracellular, suggesting that the binding of the B oligomer to the T cell plasma membrane in some way elicited calcium channel activation. Notably, the influx of calcium was not observed with cholera toxin, an AB toxin lacking mitogenic effects on the human T lymphocyte.

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“…Activation of pathways mediated by G s and/or G q/11 stimulates insulin release from β cells (3,4). The involvement of G i /G o proteins as inhibitors of insulin secretion from β cells was originally uncovered in studies on the Bordetella pertussis toxin (PTX) in animals and cells (5,6). Previously called islet-activating protein (IAP), PTX was shown to lower glucose levels in the bloodstream by increasing insulin secretion from β cells (7).…”

mentioning

confidence: 99%

Augmented glucose-induced insulin release in mice lacking G _o2 , but not G _o1 or G _i proteins

Wang

Park

Bajpayee

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Insulin secretion by pancreatic β cells is a complex and highly regulated process. Disruption of this process can lead to diabetes mellitus. One of the various pathways involved in the regulation of insulin secretion is the activation of heterotrimeric G proteins. Bordetella pertussis toxin (PTX) promotes insulin secretion, suggesting the involvement of one or more of three G i and/or two G o proteins as suppressors of insulin secretion from β cells. However, neither the mechanism of this inhibitory modulation of insulin secretion nor the identity of the G i/o proteins involved has been elucidated. Here we show that one of the two splice variants of G o , G o2 , is a key player in the control of glucose-induced insulin secretion by β cells. Mice lacking G o2 α, but not those lacking α subunits of either G o1 or any G i proteins, handle glucose loads more efficiently than wild-type (WT) mice, and do so by increased glucose-induced insulin secretion. We thus provide unique genetic evidence that the G o2 protein is a transducer in an inhibitory pathway that prevents damaging oversecretion of insulin.D iabetes mellitus is characterized by abnormalities in insulin secretion that may be either a primary defect, as seen in type I diabetes, or a secondary defect, where secretion is inadequate to overcome primary insulin resistance seen in type II diabetes. In either case, individuals are hyperglycemic. Insulin is the master controller of glucose metabolism, and its release from β cells is tightly regulated. Many factors, including hormones, neuropeptides, and neurotransmitters regulate insulin secretion by activating heterotrimeric G proteins, which can control the output of insulin in response to physiological demands (1, 2). Activation of pathways mediated by G s and/or G q/11 stimulates insulin release from β cells (3, 4). The involvement of G i /G o proteins as inhibitors of insulin secretion from β cells was originally uncovered in studies on the Bordetella pertussis toxin (PTX) in animals and cells (5, 6). Previously called islet-activating protein (IAP), PTX was shown to lower glucose levels in the bloodstream by increasing insulin secretion from β cells (7). The enhanced secretion resulted from the removal of tonic inhibition exerted by neurotransmitters/hormones, including adrenaline (8), galanin (9), and ghrelin (10). PTX catalyzes the ADP ribosylation of a carboxyl-terminal cysteine present in the α subunits of the G protein subgroup now referred to as G i /G o (11). This event causes these G proteins to become uncoupled from receptors and thereby disrupts the signal transduction process. The nonsensory PTX-sensitive G i /G o G proteins encompass three G i 's (G i1 , G i2 , and G i3 ), and two G o 's (G o1 and G o2 ). The α subunits of G i and G o display extensive homology and are functionally similar as they can be activated by the same or similar receptors and appear to signal to partially overlapping sets of effectors (12). This has raised questions whether the individual G i and G o proteins function dis...

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Islets-Activating Protein (IAP) in Bordetella pertussis that Potentiates Insulin Secretory Responses of Rats

Cited by 178 publications

References 0 publications

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

Human T lymphocyte mitogenesis in response to the B oligomer of pertussis toxin is associated with an early elevation in cytosolic calcium concentrations

Augmented glucose-induced insulin release in mice lacking G _o2 , but not G _o1 or G _i proteins

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Islets-Activating Protein (IAP) in Bordetella pertussis that Potentiates Insulin Secretory Responses of Rats

Cited by 178 publications

References 0 publications

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

The Inhibitory G Protein G<sub>i</sub> Identified as Pertussis Toxin-Catalyzed ADP-Ribosylation

Human T lymphocyte mitogenesis in response to the B oligomer of pertussis toxin is associated with an early elevation in cytosolic calcium concentrations

Augmented glucose-induced insulin release in mice lacking G o2 , but not G o1 or G i proteins

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Augmented glucose-induced insulin release in mice lacking G _o2 , but not G _o1 or G _i proteins