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Glutamine deprivation induces metabolic adaptations associated with beta cell dysfunction and exacerbate lipotoxicity
- Source :
- Molecular and cellular endocrinology. 491
- Publication Year :
- 2019
-
Abstract
- Studies have reported that plasma glutamine is reduced in type 2 diabetes (T2D) patients. Glutamine supplementation improves glycaemic control, however the mechanisms are unclear. Here, we evaluated in vitro the pancreatic beta cell bioenergetic and insulin secretory responses to various levels of glutamine availability, or treatment in the presence of an inhibitor of intracellular glutamine metabolism. The impact of glutamine deprivation to the pathological events induced by the saturated fatty acid palmitate was also investigated. Glutamine deprivation induced a reduction in mitochondrial respiration and increase in glucose uptake and utilization. This phenotype was accompanied by impairment in beta cell function, as demonstrated by diminished insulin production and secretion, and activation of the unfolded protein response pathway. Palmitate led to insulin secretory dysfunction, loss of viability and apoptosis. Importantly, glutamine deprivation significantly exacerbated these phenotypes, suggesting that low glutamine levels could participate in the process of beta cell dysfunction in T2D.
- Subjects :
- 0301 basic medicine
Blood Glucose
Male
medicine.medical_specialty
medicine.medical_treatment
Glucose uptake
Glutamine
Palmitates
030209 endocrinology & metabolism
Apoptosis
Biochemistry
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
Insulin-Secreting Cells
medicine
Animals
Insulin
Secretion
Rats, Wistar
Molecular Biology
Chemistry
Mitochondria
Rats
Oxidative Stress
030104 developmental biology
Lipotoxicity
Saturated fatty acid
Beta cell
Energy Metabolism
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 18728057
- Volume :
- 491
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular endocrinology
- Accession number :
- edsair.doi.dedup.....3b0301ccc52533c7a2e1f62059aa338b