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Dysregulation of Gl...
Dysregulation of Glucagon Secretion by Hyperglycemia-Induced Sodium-Dependent Reduction of ATP Production
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- Knudsen, J. G. (author)
- University of Oxford
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- Hamilton, Alexander (author)
- University of Oxford
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- Ramracheya, R. (author)
- University of Oxford
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- Tarasov, A. I. (author)
- University of Oxford
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- Brereton, M. (author)
- University of Oxford
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Haythorne, E. (author)
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- Chibalina, M. V. (author)
- University of Oxford
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- Spégel, Peter (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Zhang, Q. (author)
- University of Oxford
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Ashcroft, F. M. (author)
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- Adam, J. (author)
- University of Oxford
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- Rorsman, Patrik, 1959 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Sahlgrenska Academy,University of Oxford
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 29:2
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their beta cells (Fh1 beta KO 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 alpha cells from hyperglycemic Fh1 beta KO and beta-V59M gain-of-function K-ATP channel mice, diabetic Goto-Kakizaki rats, and patients with type 2 diabetes. Succination is also observed in renal tubular cells and cardiomyocytes from hyperglycemic Fh1 beta KO mice, suggesting that the model can be extended to other SGLT-expressing cells and may explain part of the spectrum of diabetic complications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- pancreatic beta-cells
- fumarate hydratase
- alpha
- dehydrogenase
- succination
- inhibition
- metabolism
- ph
- inactivation
- transport
- Cell Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Knudsen, J. G.
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Hamilton, Alexan ...
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Ramracheya, R.
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Tarasov, A. I.
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Brereton, M.
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Haythorne, E.
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show more...
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Chibalina, M. V.
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Spégel, Peter
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Mulder, Hindrik
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Zhang, Q.
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Ashcroft, F. M.
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Adam, J.
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Rorsman, Patrik, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Cell Metabolism
- By the university
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University of Gothenburg
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Lund University