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MiR-335 overexpress...
MiR-335 overexpression impairs insulin secretion through defective priming of insulin vesicles
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- Salunkhe, Vishal A. (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Beckman Research Institute of City of Hope,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Ofori, Jones K. (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Gandasi, Nikhil R (author)
- Uppsala universitet,Uppsala University,Institutionen för medicinsk cellbiologi
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- Salö, Sofia A. (author)
- Lund University,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Hansson, Sofia (author)
- Lund University,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Andersson, Markus E. (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Wendt, Anna (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Barg, Sebastian (author)
- Uppsala universitet,Uppsala University,Institutionen för medicinsk cellbiologi
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- Esguerra, Jonathan L.S. (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci Malmo, Islet Cell Exocytosis, CRC 91-11,SUS Malmo,Box 50332, S-20213 Malmo, Sweden.
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(creator_code:org_t)
- 2017-11-09
- 2017
- English.
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In: Physiological Reports. - : Wiley. - 2051-817X. ; 5:21
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Abstract
Subject headings
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- MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335- 5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca2+-dependent exocytosis. We found that the expression of miR-335 negatively correlated with secretion index in human islets of individuals with prediabetes. Overexpression of miR-335 in human KndoC- (βH\ and in rat INS-1 832/13 cells (OE335) resulted in decreased glucose-sti- mulated insulin secretion, and OE335 cells showed concomitant reduction in three exocytotic proteins: SNAP25, Syntaxin-binding protein 1 (STXBPl), and synaptotagmin 11 (SYTll). Single-cell capacitance measurements, complemented with TIRF microscopy of the granule marker NPY-mEGFP demonstrated a significant reduction in exocytosis in OE335 cells. The reduction was not associated with defective docking or decreased Ca2+ current More likely, it is a direct consequence of impaired priming of already docked granules. Earlier reports have proposed reduced granular priming as the cause of reduced first-phase insulin secretion during prediabetes. Here, we show a specific role of miR-335 in regulating insulin secretion during this transition period. Moreover, we can conclude that miR-335 has the capacity to modulate insulin secretion and Ca2+-dependent exocytosis through effects on granular priming.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- 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 -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Beta cell
- Exocytosis
- Insulin secretion
- MicroRNA
- Patch-clamp
- SNAP25
- STXBP1
- TIRF
- Type 2 Diabetes
- Beta cell
Publication and Content Type
- art (subject category)
- ref (subject category)
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Salunkhe, Vishal ...
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Ofori, Jones K.
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Gandasi, Nikhil ...
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Salö, Sofia A.
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Hansson, Sofia
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Andersson, Marku ...
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Wendt, Anna
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Barg, Sebastian
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Esguerra, Jonath ...
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Eliasson, Lena
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Uppsala University