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Paracrine control o...
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes.
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- Omar-Hmeadi, Muhmmad (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Barg
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- Lund, Per-Eric (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Gandasi, Nikhil (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Tengholm, Anders, 1971- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Barg, Sebastian, 1969- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- 2020-04-20
- 2020
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Abstract
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- Glucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
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)
Publication and Content Type
- ref (subject category)
- art (subject category)
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