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Absence of Shb impa...
Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets
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- Alenkvist, Ida (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Dyachok, Oleg (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Tian, Geng (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Li, Jia (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Mehrabanfar, Saba (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Jin, Yang (författare)
- Uppsala universitet,Institutionen för neurovetenskap
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- Birnir, Bryndis (författare)
- Uppsala universitet,Fysiologi
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- Tengholm, Anders (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Welsh, Michael (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- 2014
- 2014
- Engelska.
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 223:3, s. 267-275
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The Src homology-2 domain containing protein B (SHB) has previously been shown to function as a pleiotropic adapter protein, conveying signals from receptor tyrosine kinases to intracellular signaling intermediates. The overexpression of Shb in β-cells promotes β-cell proliferation by increased insulin receptor substrate (IRS) and focal adhesion kinase (FAK) activity, whereas Shb deficiency causes moderate glucose intolerance and impaired first-peak insulin secretion. Using an array of techniques, including live-cell imaging, patch-clamping, immunoblotting, and semi-quantitative PCR, we presently investigated the causes of the abnormal insulin secretory characteristics in Shb-knockout mice. Shb-knockout islets displayed an abnormal signaling signature with increased activities of FAK, IRS, and AKT. β-catenin protein expression was elevated and it showed increased nuclear localization. However, there were no major alterations in the gene expression of various proteins involved in the β-cell secretory machinery. Nor was Shb deficiency associated with changes in glucose-induced ATP generation or cytoplasmic Ca(2) (+) handling. In contrast, the glucose-induced rise in cAMP, known to be important for the insulin secretory response, was delayed in the Shb-knockout compared with WT control. Inhibition of FAK increased the submembrane cAMP concentration, implicating FAK activity in the regulation of insulin exocytosis. In conclusion, Shb deficiency causes a chronic increase in β-cell FAK activity that perturbs the normal insulin secretory characteristics of β-cells, suggesting multi-faceted effects of FAK on insulin secretion depending on the mechanism of FAK activation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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