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Impaired cAMP gener...
Impaired cAMP generation contributes to defective glucose-stimulated insulin secretion after long-term exposure to palmitate
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- Tian, Geng (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Sol, Eri Maria (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Xu, Yunjian (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Shuai, Hongyan (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Tengholm, Anders (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- 2014-10-03
- 2015
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:3, s. 904-915
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://diabetes.dia...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- Chronic palmitate exposure impairs glucose-stimulated insulin secretion and other aspects of β-cell function but the underlying mechanisms are not known. Using various live-cell fluorescence imaging approaches we show here that long-term palmitate treatment influences cAMP signaling in pancreatic β-cells. Glucose stimulation of mouse and human β-cells induced oscillations of the sub-plasma-membrane cAMP concentration but after 48 h exposure to palmitate, most β-cells failed to increase cAMP in response to glucose. In contrast, GLP-1-triggered cAMP formation and glucose- and depolarization-induced increases in cytoplasmic Ca2+ concentration were unaffected by the fatty acid treatment. Insulin secretion from control β-cells was pulsatile but the response deteriorated after long-term palmitate exposure. Palmitate-treated mouse islets showed reduced expression of adenylyl cyclase 9 and knockdown of this protein in insulinoma cells reduced the glucose-stimulated cAMP response and insulin secretion. We conclude that impaired glucose-induced generation of cAMP is an important determinant of defective insulin secretion after chronic palmitate exposure.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Diabetes
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