Glucose intolerance in monosodium glutamate obesity is linked to hyperglucagonemia and insulin resistance in α cells

Abstract

Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β-cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)-obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1.25 mg/g BW). At 90 days of age, MSG-obese mice were hyperglycemic, hyperinsulinemic, and hyperglucagonemic and had lost the capacity to increase their insulin/glucagon ratio when transitioning from the fasting to fed state, exacerbating hepatic glucose output. Furthermore, hepatic protein expressions of phosphorylated (p)-protein kinase A (PKA) and cAMP response element-binding protein (pCREB), and of phosphoenolpyruvate carboxykinase (PEPCK) enzyme were higher in fed MSG, before and after glucagon stimulation. Increased pPKA and phosphorylated hormone-sensitive lipase content were also observed in white fat of MSG. MSG islets hypersecreted glucagon in response to 11.1 and 0.5 mmol/L glucose, a phenomenon that persisted in the presence of insulin. Additionally, MSG α cells were hypertrophic displaying increased α-cell mass and immunoreactivity to phosphorylated mammalian target of rapamycin (pmTOR) protein. Therefore, severe glucose intolerance in MSG-obese mice was associated with increased hepatic glucose output, in association with hyperglucagonemia, caused by the refractory actions of glucose and insulin in α cells and via an effect that may be due to enhanced mTOR activation.

Biochemical effects of Short–long Term Extensive Administration of Monosodium Glutamate and Soybean on Wistar Rats

“…Some researchers also proposed that a significant increase in blood glucose after MSG administration was probably because of its conversion glutamic acid moiety of MSG to oxalacetate by D-amino acid oxidase thereby producing glucogenic precursor [6]. Also, in support of the findings of this study, Araujo et al, [34] suggested that the hyperglycaemic effect of MSG could arise as a result of poor ability to oxidize glutamic acid in the pancreatic cells and that MSG acts via phosphoenolpyruvate carboxykinase in decreasing blood glucose. The study of Dayer and Dayer,[35] validates the findings of this present study, showing no significant alterations in plasma insulin concentration in short term administration of low and medium doses of MSG which was attributed to the low stimulation of glutamate receptors in β pancreatic cell [31].…”

D-Pinitol Increases Insulin Secretion and Regulates Hepatic Lipid Metabolism in Msg-Obese Mice

“…As previously demonstrated (Araujo et al 2019, Bonfleur et al 2015, Macho et al 2000, Nardelli et al 2011, Oida et al 1984, from 30 to 120 days of age, MSG mice displayed similar BW (Fig. 1b and 1c), food ( Fig.…”

“…Food consumption was measured once a week and water intake was measured every two days; results are expressed as the food or water ingestion per day. Feed efficiency was obtained by the ratio from the total BW gained, divided by the total food consumption before or during the treatment period (Araujo et al 2019).…”

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Thus, circulating glutamate is positively related to visceral obesity and posterior development of MetS [154]. In a pre-clinical study, IR was correlated with glutamate in mice treated with monosodium glutamate to develop obesity [49]. Moreover, in obese morbid patients, those with pre-diabetes were found to have higher serum glutamate levels compared to non-diabetic controls.…”