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Tight coupling betw...
Tight coupling between glucose and mitochondrial metabolism in clonal beta-cells is required for robust insulin secretion.
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- Malmgren, Siri (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Lund University Research Groups
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- Nicholls, David (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Taneera, Jalal (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Bacos, Karl (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Koeck, Thomas (author)
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- Tamaddon, Ashkan (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Wibom, Rolf (author)
- Karolinska Institutet
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Sharoyko, Vladimir (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: Journal of Biological Chemistry. - 1083-351X. ; 284, s. 32395-32404
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Abstract
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- The biochemical mechanisms underlying glucose-stimulated insulin secretion from pancreatic beta-cells are not completely understood. To identify metabolic disturbances in beta-cells that impair glucose-stimulated insulin secretion, we compared two INS-1-derived clonal beta-cell lines, which are glucose-responsive (832/13) or glucose-unresponsive (832/2). We found that despite a marked impairment of glucose-stimulated insulin secretion, 832/2 cells exhibited a higher rate of glycolysis. Still, no glucose-induced increases in respiratory rate, ATP production or respiratory chain complex I, III and IV activities were seen in the 832/2 cells. Instead, 832/2 cells, which expressed lactate dehydrogenase, released lactate regardless of ambient glucose concentrations. In contrast, the glucose-responsive 832/13 line lacked lactate dehydrogenase and did not produce lactate. Accordingly, in 832/2 cells mRNA expression of genes for glycolytic enzymes were up-regulated, whereas mitochondria-related genes were down-regulated. In human islets, mRNA expression of genes such as lactate dehydrogenase A and hexokinase I correlated positively with long-term glucose homeostasis reflected by HbA1c levels, while that of Slc2a2 (GLUT2) correlated negatively with Hb1Ac. We conclude that tight metabolic regulation enhancing mitochondrial metabolism and restricting glycolysis in 832/13 cells is required for clonal beta-cells to secrete insulin robustly in response to glucose. Moreover, a similar expression pattern of genes controlling glycolytic and mitochondrial metabolism in clonal beta-cells and human islets was observed, suggesting that a similar prioritization of mitochondrial metabolism is required in healthy human beta-cells. The 832 beta-cell lines may be helpful tools to resolve metabolic perturbations occurring in Type 2 Diabetes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Malmgren, Siri
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Nicholls, David
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Taneera, Jalal
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Bacos, Karl
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Koeck, Thomas
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Tamaddon, Ashkan
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show more...
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Wibom, Rolf
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Groop, Leif
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Ling, Charlotte
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Mulder, Hindrik
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Sharoyko, Vladim ...
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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 ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Biolo ...
- By the university
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Lund University
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Karolinska Institutet