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Impaired glucose-st...
Impaired glucose-stimulated insulin secretion, enhanced IP insulin tolerance and increased {beta}-cell mass in mice lacking the p110{gamma} isoform of PI3-kinase.
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- MacDonald, Patrick (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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Joseph, J. W. (author)
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Yau, D. (author)
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Diao, J. (author)
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Asghar, Z. (author)
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Dai, F. (author)
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Oudit, G. Y. (author)
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Patel, M. M. (author)
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Backx, P. H. (author)
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Wheeler, M. B. (author)
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(creator_code:org_t)
- The Endocrine Society, 2004
- 2004
- English.
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 145:9, s. 4078-4083
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Abstract
Subject headings
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- Phosphoinositide 3-kinase (PI3 kinase) has been implicated in G protein-coupled receptor regulation of pancreatic ß-cell growth and glucose-stimulated insulin secretion. The G protein-activated p110{gamma} isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets. In 7- to 10-wk-old mice, knockout of p110{gamma} reduced the plasma insulin response to ip glucose injection and impaired first and second phase glucose-stimulated insulin secretion from pancreata perfused ex vivo. The p110{gamma} –/– mice responded to preinjection with the glucagon-like peptide-1 receptor agonist exendin 4, such that plasma glucose and insulin responses to ip glucose injection were not different from wild types. Mice lacking p110{gamma} were not diabetic and were only slightly glucose intolerant (ip glucose injection) compared with wild types, in part due to enhanced responsiveness to insulin as determined by an ip insulin tolerance test. Despite severely reduced insulin secretion in these animals, the p110{gamma} –/– mice had greater pancreatic insulin content, and an increased ß-cell mass due to ß-cell hypertrophy. These surprising results suggest that the G protein-coupled p110{gamma} isoform of PI3 kinase is not central to the development or maintenance of sufficient ß-cell mass but positively regulates glucose-stimulated insulin secretion.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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MacDonald, Patri ...
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Joseph, J. W.
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Yau, D.
-
Diao, J.
-
Asghar, Z.
-
Dai, F.
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show more...
-
Oudit, G. Y.
-
Patel, M. M.
-
Backx, P. H.
-
Wheeler, M. B.
-
show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Endocrinology
- By the university
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Lund University