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

Thiago R. Araujo, Joel A. da Silva, Jean F. Vettorazzi, Israelle N. Freitas, Camila Lubaczeuski, Emily A. Magalhães, Juliana N. Silva, Elane S. Ribeiro, Antonio C. Boschero, Everardo M. Carneiro, Maria L. Bonfleur, Rosane Aparecida Ribeiro

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7019-7031
Number of pages13
JournalJournal of Cellular Physiology
Issue number5
StatePublished - May 2019
Externally publishedYes


  • glucagon secretion
  • hepatic glucose output
  • lipolysis
  • obesity

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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