A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat pancreatic islets and brain

Katoh, Junichi; Taniguchi, Hiroshi; Ogura, Mitsuo; Kasuga, Masato; Okada, Yasuhiro

doi:10.1007/bf01931099

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…Inhibition of GAD67 activity abolishes glucosestimulated insulin secretion (GSIS) in β-cells and young and aged islets Because GAD67 expression is significantly upregulated in response to increased glucose concentrations, we examined whether GAD67 activity affects the capacity of β-cells and islets to secrete insulin. We treated the β-TC6 cell line with 3-mercaptopropionic acid (3-MPA), a potent competitive inhibitor of GADs that is commonly used to modify GAD activity in rodent pancreatic islets and brain, [21][22][23] and did not observe effects on cell viability below 50 μM 3-MPA (Supplementary Figure 3A and B). Similarly, we tested primary islets isolated from young and aged mice.…”

Section: Elevated Gad67 Expression Does Not Cause Autoimmune Destructmentioning

confidence: 99%

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Cho

Lee

et al. 2019

Islets

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Pancreatic islets play an essential role in regulating blood glucose levels. Age-dependent development of glucose intolerance and insulin resistance results in hyperglycemia, which in turn stimulates insulin synthesis and secretion from aged islets, to fulfill the increased demand for insulin. However, the mechanism underlying enhanced insulin secretion remains unknown. Glutamic acid decarboxylase 67 (GAD67) catalyzes the conversion of glutamate into γaminobutyric acid (GABA) and CO 2. Both glutamate and GABA can affect islet function. Here, we investigated the role of GAD67 in insulin secretion in young (3 month old) and aged (24 month old) C57BL/6J male mice. Unlike young mice, aged mice displayed glucose-intolerance and insulin-resistance. However, aged mice secreted more insulin and showed lower fed blood glucose levels than young mice. GAD67 levels in primary islets increased with aging and in response to high glucose levels. Inhibition of GAD67 activity using a potent inhibitor of GAD, 3-mercaptopropionic acid, abrogated glucose-stimulated insulin secretion from a pancreatic β-cell line and from young and aged islets. Collectively, our results suggest that blood glucose levels regulate GAD67 expression, which contributes to β-cell responses to impaired glucose homeostasis caused by advanced aging.

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Section: Elevated Gad67 Expression Does Not Cause Autoimmune Destructmentioning

confidence: 99%

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Cho

Lee

et al. 2019

Islets

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“…24 Furthermore, a number of interesting data concerning the expression and physiological functions of the GAD isoenzymes from mammalian tissues have been published in recent years. [25][26][27][28] Other authors describe the influence of certain convulsants [29][30][31] and anticonvulsants 16,32 on GABA levels in brain tissues. According to an early report, the 4′-substituted vitamin B 6 derivative 4′-deoxypyridoxine (4, Figure 1) was shown to be a potent inhibitor of GAD.…”

Section: Introductionmentioning

confidence: 99%

“…According to experiments with recombinant enzymes, GAD 65kDa seems to be more responsive than GAD 67kDa , but the differences have not as yet been characterized − Other authors describe the influence of certain convulsants − and anticonvulsants , on GABA levels in brain tissues. According to an early report, the 4‘-substituted vitamin B 6 derivative 4‘-deoxypyridoxine ( 4 , Figure ) was shown to be a potent inhibitor of GAD .…”

Section: Introductionmentioning

confidence: 99%

Properties and Interaction of Heterologously Expressed Glutamate Decarboxylase Isoenzymes GAD_65kDaand GAD_67kDafrom Human Brain with Ginkgotoxin and Its 5‘-Phosphate

et al. 2001

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Two isoforms of glutamate decarboxylase (GAD(65kDa) and GAD(67kDa)) from human brain, which had previously been overexpressed in Escherichia coli as fusion proteins containing a glutathione-S-transferase domain, were purified by affinity chromatography on glutathione Sepharose 4B. Both isoforms were also expressed in Saccharomyces cerevisiae. After modification of a HPLC based assay, the enzymes were characterized with respect to their biochemical properties. Comparison of kinetic data, pH, and temperature optima as well as of the mode of interaction with pyridoxal phosphate as a cofactor revealed several significant differences between the two isoenzymes reflecting their somewhat different physiological and molecular features. Investigation of the influence of 4'-O-methylpyridoxine (ginkgotoxin) (1), a neurotoxin occurring in Ginkgo biloba L., on the different isoenzymes, indicates that the phosphorylated form of the toxin, 4'-O-methylpyridoxine-5'-phosphate (2), decreases GAD(65kDa) activity, although in unphysiologically high concentrations, whereas GAD(67kDa) activity seems to be hardly affected.

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γ-Aminobutyric acid (GABA) signalling in plants

Ramesh

Tyerman

Gilliham

et al. 2016

Cell. Mol. Life Sci.

246

155

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The role of γ-aminobutyric acid (GABA) as a signal in animals has been documented for over 60 years. In contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last year that a mechanism by which this could occur was identified-a plant 'GABA receptor' that inhibits anion passage through the aluminium-activated malate transporter family of proteins (ALMTs). ALMTs are multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of ALMT activity could function as a signal that modulates plant growth, development, and stress response. In this review, we compare and contrast the plant 'GABA receptor' with mammalian GABA receptors in terms of their molecular identity, predicted topology, mode of action, and signalling roles. We also explore the implications of the discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant physiology, and predict the possibility that there are other GABA interaction sites in the N termini of ALMT proteins through in silico evolutionary coupling analysis; we also explore the potential interactions between GABA and other signalling molecules.

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A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat pancreatic islets and brain

Cited by 3 publications

References 19 publications

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Properties and Interaction of Heterologously Expressed Glutamate Decarboxylase Isoenzymes GAD_65kDaand GAD_67kDafrom Human Brain with Ginkgotoxin and Its 5‘-Phosphate

γ-Aminobutyric acid (GABA) signalling in plants

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A convulsant, 3-mercaptopropionic acid, decreases the level of GABA and GAD in rat pancreatic islets and brain

Cited by 3 publications

References 19 publications

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Glutamate decarboxylase 67 contributes to compensatory insulin secretion in aged pancreatic islets

Properties and Interaction of Heterologously Expressed Glutamate Decarboxylase Isoenzymes GAD65kDaand GAD67kDafrom Human Brain with Ginkgotoxin and Its 5‘-Phosphate

γ-Aminobutyric acid (GABA) signalling in plants

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Properties and Interaction of Heterologously Expressed Glutamate Decarboxylase Isoenzymes GAD_65kDaand GAD_67kDafrom Human Brain with Ginkgotoxin and Its 5‘-Phosphate