Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia

Yu, Tingting; Jiang, Zhonghua; Liu, Li; Fan, Zhining

doi:10.3892/etm.2017.5670

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…These studies found that “if the delivery of insulin or GABA plus insulin in rats with hypoglycemia is terminated, β -cells are stimulated and signal the α -cells to secrete glucagon. Thus, the detection of a sudden decrease in zinc levels by β -cells as well as a decrease in GABA in ... circulation induces signaling to α -cells to stimulate them to secrete glucagon” [ 106 ]. These studies also show that GABA decreases beta cell secretory activity mainly in response to glucose.…”

Section: Discussionmentioning

confidence: 99%

The Aging GABAergic System and Its Nutritional Support

Mills¹

2021

Journal of Nutrition and Metabolism

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Aging is associated with a decline in hormones and an associated decline in GABAergic function and calcium and ion current dysregulation. Neurosteroid hormones act as direct calcium channel blockers, or they can act indirectly on calcium channels through their interaction with GABA receptors. The calcium channel dysfunction associated with hormone loss further leads to an excitatory cell state, which can ultimately lead to cell death. The calcium theory of aging posits that cellular mechanisms, which maintain the homeostasis of cytosol Ca2+ concentration, play a key role in brain aging and that sustained changes in Ca2+ homeostasis provide the final common pathway for age-associated brain changes. There is a link between hormone loss and calcium dysregulation. Loss of calcium regulation associated with aging can lead to an excitatory cell state, primarily in the mitochondria and nerve cells, which can ultimately lead to cell death if not kept in check. A decline in GABAergic function can also be specifically tied to declines in progesterone, allopregnanolone, and DHEA levels associated with aging. This decline in GABAergic function associated with hormone loss ultimately affects GABAergic inhibition or excitement and calcium regulation throughout the body. In addition, declines in GABAergic function can also be tied to vitamin status and to toxic chemicals in the food supply. The decline in GABAergic function associated with aging has an effect on just about every body organ system. Nutritional support of the GABAergic system with supportive foods, vitamins, and GABA or similar GABA receptor ligands may address some of the GABAergic dysfunction associated with aging.

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Section: Discussionmentioning

confidence: 99%

The Aging GABAergic System and Its Nutritional Support

Mills¹

2021

Journal of Nutrition and Metabolism

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“…Gamma-aminobutyric acid, commonly referred to as GABA, possesses several noteworthy physiological functions within the human system. As a non-protein amino acid derived through glutamic acid decarboxylase enzymatic action, GABA elicits hypotensive, neurological signalling, anxiolytic, and diuretic responses [6]. It operates as an inhibitory neurotransmitter within the sympathetic nervous system, conferring anti-diabetic and anti-hypersensitivity effects [7].…”

Section: Introductionmentioning

confidence: 99%

Biological activities of gaba-producing probiotics from fermented panchagavya

Varsha,

Thamarai Selvi

2024

J. Phys.: Conf. Ser.

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Panchagavya, a venerable elixir from the Ayurvedic tradition, merits scholarly inspection. It denotes the sacred offerings of cow’s milk, urine, dung, ghee and curd, holding medicinal import within Ayurveda’s ancient practices. This study aims to illuminate differences between probiotic variants V2 and V7, through findings on their pharmacological applications and biochemical concentrations. It is proposed that fermented panchagavya’s psychobiotic strains may exhibit favorable reactions worth examining. Chiefly, the organic synthesis of neurotransmitters by beneficial bacteria is of interest. The regulatory neurotransmitter gamma-aminobutyric acid (GABA) could potentially be generated by a panchagavya-derived probiotic. Through serial dilution culture of bacteria obtained from fermented panchagavya, their growth and GABA formation, as evaluated by thin-layer chromatography and ultraviolet-visible spectrometric analysis, are observed. Strain V2 demonstrates promising pharmacological properties including antioxidant, anti-inflammatory, anti-diabetic and anti-obesity effects, as well as inhibition of albumin denaturation and heat-induced hemolysis. It presents a higher concentration of such activities than V7. Biochemical tests further indicate V2’s larger percentage of GABA synthesis, supporting prospective therapeutic applications. After sequencing selected strains to explore psychobiotic functioning, their isolation holds medical import as GABA-producing beneficial bacteria from fermented panchagavya.

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“…GABA has been thought to ameliorate diabetic symptoms [16,17]. Despite accumulated knowledge, the interactions between GABA and zinc in insulin secretion are not fully understood [18]. Furthermore, it is important to understand whether exogenous GABA supplementation can potentially be utilized as an inducer of GABA-mediated insulin secretion in SHED β-cells for therapeutic use.…”

Section: Introductionmentioning

confidence: 99%

Insulin Secretion by β-Cell-Like Cells Derived from Pulp Stem Cells Depends on Augmented Cytosolic Zinc Levels than GABA Levels

2020

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Background: Stem cells harvested from human exfoliated deciduous teeth (SHED) are pluripotent and can be differentiated into insulin-secreting β-cells, i.e., SHED β-cells. Previously, we showed that zinc upregulates insulin secretion from SHED β-cells, potentially providing an extra source for insulin. Rationale: In this study, we determined the role of ionotropic γ-aminobutyric acid A (GABAA) receptor in zinc-enhanced insulin secretion from SHED β-cells. Autocrine/paracrine activation of GABAA receptors by GABA elevates calcium influx in pancreatic β-cells, in which intracellular chloride is maintained at high levels. Method and Findings: Differentiating SHED into SHED β-cells resulted in an increase in the expression of GABAA receptor subunits and Zrt-/irt-like protein3 (ZIP3), a zinc uptake transporter. Zinc pretreatment elevated the insulin gene transcription, whereas knockdown of ZIP3 reduced levels of intracellular zinc, and concomitantly reduced insulin secretion by SHED β-cells. Zinc-pretreated SHED β-cells exhibited a GABA-induced increase in Ca2+ influx, detected with a ratiometric calcium-sensitive dye, suggesting zinc-mediated regulation of GABAA receptors. Conclusion: Our results indicate that elevated levels of zinc and GABAA receptors are indispensable for efficient insulin secretion by SHED β-cells. These findings suggest an opportunity for using SHED β-cells for treating diabetes.

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Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia

Cited by 6 publications

References 24 publications

The Aging GABAergic System and Its Nutritional Support

The Aging GABAergic System and Its Nutritional Support

Biological activities of gaba-producing probiotics from fermented panchagavya

Insulin Secretion by β-Cell-Like Cells Derived from Pulp Stem Cells Depends on Augmented Cytosolic Zinc Levels than GABA Levels

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