例如："lncRNA", "apoptosis", "WRKY"

Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production.

Cell Metab. 2019 Feb 05;29(2):430-442.e4. Epub 2018 Nov 08
Jakob G Knudsen 1 , Alexander Hamilton 1 , Reshma Ramracheya 1 , Andrei I Tarasov 1 , Melissa Brereton 2 , Elizabeth Haythorne 2 , Margarita V Chibalina 1 , Peter Spégel 3 , Hindrik Mulder 4 , Quan Zhang 1 , Frances M Ashcroft 2 , Julie Adam 5 , Patrik Rorsman 6
Jakob G Knudsen 1 , Alexander Hamilton 1 , Reshma Ramracheya 1 , Andrei I Tarasov 1 , Melissa Brereton 2 , Elizabeth Haythorne 2 , Margarita V Chibalina 1 , Peter Spégel 3 , Hindrik Mulder 4 , Quan Zhang 1 , Frances M Ashcroft 2 , Julie Adam 5 , Patrik Rorsman 6
+ et al

[No authors listed]

Author information
  • 1 Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
  • 2 Department of Physiology, Anatomy & Genetics, Parks Road, Oxford OX1 3PT, UK.
  • 3 Centre for Analysis and Synthesis, Lund University Diabetes Centre, Department of Chemistry, Naturvetarvägen 14, Lund 221 00, Sweden.
  • 4 Unit of Molecular Metabolism, Lund University Diabetes Centre, Department of Clinical Research in Malmö, Jan Waldenströms Gata 35, Malmö 205 02, Sweden.
  • 5 Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Nuffield Department of Clinical Medicine, University of Oxford, NDM Research Building, Oxford OX3 7FZ, UK. Electronic address: julie.adam@ndm.ox.ac.uk.
  • 6 Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Metabolic Research, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Göteborg, Box 433, Göteborg 405 30, Sweden. Electronic address: patrik.rorsman@drl.ox.ac.uk.

摘要

Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion. Protein succination, reflecting reduced activity of fumarase, is observed in α cells from hyperglycemic Fh1βKO and β-V59M gain-of-function KATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1βKO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.

KEYWORDS: Fh1, diabetes, glucagon, sodium-glucose co-transport, succination

© 2017 biocloud.net版权所有 ICP证：京10042835号