title: GLP-1 secretion by microglial cells and decreased CNS expression in obesity.
abstract: BACKGROUND
  Type 2 diabetes (T2D) is a strong risk factor for developing neurodegenerative pathologies. T2D patients have a deficiency in the intestinal incretin hormone GLP-1, which has been shown to exert neuroprotective and anti-inflammatory properties in the brain.
  
  
  METHODS
  Here we investigate potential sources of GLP-1 in the CNS and the effect of diabetic conditions on the proglucagon mRNA expression in the CNS. The obese mouse model ob/ob, characterized by its high levels of free fatty acids, and the microglia cell line BV-2 were used as models. mRNA expression and protein secretion were analyzed by qPCR, immunofluorescence and ELISA.
  
  
  RESULTS
  We show evidence for microglia as a central source of GLP-1 secretion. Furthermore, we observed that expression and secretion are stimulated by cAMP and dependent on microglial activation state. We also show that insulin-resistant conditions reduce the central mRNA expression of proglucagon.
  
  
  CONCLUSIONS
  The findings that microglial mRNA expression of proglucagon and GLP-1 protein expression are affected by high levels of free fatty acids and that both mRNA expression levels of proglucagon and secretion levels of GLP-1 are affected by inflammatory stimuli could be of pathogenic importance for the premature neurodegeneration and cognitive decline commonly seen in T2D patients, and they may also be harnessed to advantage in therapeutic efforts to prevent or treat such disorders.
authors.affiliation: Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm 11883, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Kappe
authors.forename: Linda M
authors.initials: LM
authors.lastname: Tracy
authors.forename: Cesare
authors.initials: C
authors.lastname: Patrone
authors.forename: Kerstin
authors.initials: K
authors.lastname: Iverfeldt
authors.forename: Åke
authors.initials: Å
authors.lastname: Sjöholm
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D002688:Chitinases / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D017628:Microglia / Q000378:metabolism*; D009765:Obesity / Q000473:pathology*; D010168:Palmitates / Q000494:pharmacology; D010940:Plant Proteins; D011134:Polysaccharides / Q000494:pharmacology; D052336:Proglucagon / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D010168:Palmitates; D010940:Plant Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D002688:Chitinases; C119825:chitinase C; C544448:Arg1 protein, mouse; D001119:Arginase