Sökning: WFRF:(McLaughlin Samuel B)
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Loss of tetraspanin...
Loss of tetraspanin-7 expression reduces pancreatic beta-cell exocytosis Ca2+ sensitivity but has limited effect on systemic metabolism
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McLaughlin, K. (författare)
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- Acreman, Samuel (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Nawaz, S. (författare)
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Cutteridge, J. (författare)
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Clark, A. (författare)
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Knudsen, J. G. (författare)
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Denwood, G. (författare)
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Spigelman, A. F. (författare)
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Fox, J. E. M. (författare)
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Singh, S. P. (författare)
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MacDonald, P. E. (författare)
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Hastoy, B. (författare)
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Zhang, Q. (författare)
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(creator_code:org_t)
- 2022-10-31
- 2022
- Engelska.
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 39:12
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: Tetraspanin-7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate beta-cell L-type Ca-2(+) channel activity. However, the role of Tspan7 in pancreatic beta-cell function is not yet fully understood. Methods: Histological analyses were conducted using immunostaining. Whole-body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. beta-cell transmembrane currents, electrical activity and exocytosis were measured using whole-cell patch-clamping and capacitance measurements. Gene expression was studied using m RNA-sequencing and quantitative PCR. Results: Tspan7 is expressed in insulin-containing granules of pancreatic beta-cells and glucagon-producing alpha-cells. Tspan7 knockout mice (Tspan(gamma/-) mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan(gamma/- )islets have normal insulin content and glucose- or tolbutamide-stimulated insulin secretion. Depolarisation-triggered Ca2+ current was enhanced in Tspan(gamma/-) beta-cells, but beta-cell electrical activity and depolarisation-evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca2+. TSPAN7 knockdown (KD) in human pseudo-islets led to a significant reduction in insulin secretion stimulated by 20 mM Transcriptomic analyses show that TSPAN7 KD in human pseudo-islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent beta-cells, exocytotic Ca2+ sensitivity was reduced in a human beta-cell line (EndoC-beta H1) following Tspan7 KD. Conclusion: Tspan7 is involved in the regulation of Ca2+-dependent exocytosis in beta-cells. Its function is more significant in human beta-cells than their rodent counterparts.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- beta-cell
- exocytosis
- insulin
- synaptotagmin
- tetraspanin-7
- extracellular domain
- superfamily
- gene
- Endocrinology & Metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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McLaughlin, K.
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Acreman, Samuel
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Nawaz, S.
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Cutteridge, J.
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Clark, A.
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Knudsen, J. G.
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visa fler...
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Denwood, G.
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Spigelman, A. F.
-
Fox, J. E. M.
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Singh, S. P.
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MacDonald, P. E.
-
Hastoy, B.
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Zhang, Q.
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Diabetic Medicin ...
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Göteborgs universitet