Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting cells

Research output: Contribution to journalJournal articleResearchpeer-review

Camilla Kappe, Jens Juul Holst, Qimin Zhang, Ake Sjöholm

Evidence is emerging that elevated serum free fatty acids (hyperlipidemia) contribute to the pathogenesis of type-2-diabetes, and lipotoxicity is observed in many cell types. We recently published data indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting cells, where the antidiabetic drug metformin conferred protection from lipoapoptosis. The aim of the present study was to identify mechanisms involved in mediating lipotoxicity and metformin lipoprotection in GLP-1 secreting cells. These signaling events triggered by simulated hyperlipidemia may underlie reduced GLP-1 secretion in diabetic subjects, and metformin lipoprotection by metformin could explain elevated plasma GLP-1 levels in diabetic patients on chronic metformin therapy. The present study may thus identify potential molecular targets for increasing endogenous GLP-1 secretion through enhanced viability of GLP-1 secreting cells in diabetic hyperlipidemia and obesity.
Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Volume427
Issue number1
Pages (from-to)91-5
Number of pages5
ISSN0006-291X
DOIs
Publication statusPublished - 12 Oct 2012

    Research areas

  • Animals, Antioxidants, Apoptosis, Caspase 3, Cell Line, Chromans, Cytoprotection, Fatty Acids, Nonesterified, Glucagon-Like Peptide 1, Hyperlipidemias, Hypoglycemic Agents, MAP Kinase Kinase 3, MAP Kinase Kinase 4, MAP Kinase Kinase 6, Metformin, Mice, Mice, Transgenic, Palmitates, Reactive Oxygen Species, p38 Mitogen-Activated Protein Kinases

ID: 45840730