title: Progressive change of intra-islet GLP-1 production during diabetes development.
abstract: BACKGROUND
  Glucagon-like peptide 1 (GLP-1) and glucagon share the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue-specific manner. Recently, it has been shown that GLP-1 is co-expressed with glucagon in pancreatic islet cells. This study was aimed to investigate the progressive changes of GLP-1 versus glucagon production in pancreatic islets during the course of diabetes development.
  
  
  METHODS
  Both type 1 (non-obese diabetes mice) and type 2 (db/db mice) diabetes models were employed in this study. The mice were monitored closely for their diabetes progression and were sacrificed at different stages according to their blood glucose levels. GLP-1 and glucagon expression in the pancreatic islets was examined using immunohistochemistry assays. Quantitative analysis was performed to evaluate the significance of the changes.
  
  
  RESULTS
  The ratio of GLP-1-expressing cells to glucagon-expressing cells in the islets showed significant, progressive increase with the development of diabetes in db/db mice. The increase of GLP-1 expression was in agreement with the upregulation of PC1/3 expression in these cells. Interestingly, intra-islet GLP-1 expression was not significantly changed during the development of type 1 diabetes in non-obese diabetes mice.
  
  
  CONCLUSIONS
  The study demonstrated that GLP-1 was progressively upregulated in pancreatic islets during type 2 diabetes development. In addition, the data suggest clear differences in intra-islet GLP-1 production between type 1 and type 2 diabetes developments. These differences may have an effect on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches.
authors: Endocrinology Section, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, United States.
authors: Thomas J
authors: TJ
authors: O'Malley
authors: Genevieve E
authors: GE
authors: Fava
authors: Yanqing
authors: Y
authors: Zhang
authors: Vivian A
authors: VA
authors: Fonseca
authors: Hongju
authors: H
authors: Wu
mesh_terms: D000465:Algorithms; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D011236:Prediabetic State / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D045664:Proprotein Convertase 1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1
keywords: GLP-1; diabetes; islets; α-cells