The potential role of glutamate in the current diabetes epidemic

Davalli, Alberto M.; Perego, Carla; Folli, Franco

doi:10.1007/s00592-011-0364-z

Cited by 52 publications

(39 citation statements)

References 244 publications

(260 reference statements)

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“…Systemic plasma glutamate levels are elevated in several diseases that are characterized by oxidative stress and inflammation4, such as obesity31. Our data showed that plasma glutamate levels were elevated in diabetic patients and diabetic mice.…”

Section: Discussionsupporting

confidence: 49%

An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes

Huang

Peng

et al. 2017

Sci Rep

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In the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia.

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Section: Discussionsupporting

confidence: 49%

An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes

Huang

Peng

et al. 2017

Sci Rep

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“…High concentration of glutamic acid is toxic for β-cells. Excessive dietary intake of glutamate may cause obesity and insulin resistance [10]. Low levels of glycine are the result of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

An Assay of Selected Serum Amino Acids in Patients with Type 2 Diabetes Mellitus

Drábková¹,

Šanderová²,

Kovarik³

et al. 2015

Adv Clin Exp Med

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Background. Amino acids are the building blocks of proteins. In case of insulin resistance, which is typical for type 2 diabetes mellitus (T2DM), proteolysis is increased and protein synthesis is decreased; therefore, we can observe changes in the levels of amino acids in diabetics vs. non-diabetics. Objectives. The aim of this study was to find differences in the levels of selected amino acids between patients with diabetes (type 2) and a control group. Material and Methods. Amino acids were derivatized with naphthalene-2,3-dicarboxaldehyde in the presence of potassium cyanide to form fluorescent 1-cyanobenz(f)isoindole product. Amino acids derivatives were measured using a high-performance liquid chromatography with fluorescence detection. The serum levels of glucose were determined using an automatic biochemistry analyzer, glycated hemoglobin HbA1c was measured by cation exchange chromatography. Results. A total of 19 serum amino acids in T2DM patients and non-diabetics were measured. There were 9 amino acids, which were significantly different in these groups (p < 0.05). Significantly decreased levels of arginine, asparagine, glycine, serine, threonine and significantly increased levels of alanine, isoleucine, leucine, valine in diabetics were found. Conclusions. Significant difference in metabolism of amino acids between diabetics and non-diabetics were observed. The altered levels of amino acids in diabetic patients could be a suitable predictor of diabetes (Adv Clin Exp Med 2015, 24, 3, 447-451).

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“…Glutamate at high levels is well known to be toxic to the central nervous system [55], retinal neurons [56] and pancreatic islets [57]. As the fetal blood brain barrier is relatively permeable, even a slight increase in circulating glutamate has been shown to overstimulate neurons in the arcuate nucleus that can lead to metabolic dysregulation in later life [58].…”

Section: Discussionmentioning

confidence: 99%

Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

Reynolds

Sloboda

et al. 2013

PLoS ONE

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Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.

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The potential role of glutamate in the current diabetes epidemic

Cited by 52 publications

References 244 publications

An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes

An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes

An Assay of Selected Serum Amino Acids in Patients with Type 2 Diabetes Mellitus

Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

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