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• W2891879780 abstract "Of the many common genetic variants associated with type 2 diabetes, that in TCF7L2 remains the most studied because it has the greatest effect size. However, the mechanism by which this variant alters diabetes risk remains elusive. A new study adds another layer of complexity, suggesting that the effects of TCF7L2 are context-dependent, and highlights a novel interaction that might bias a β-cell to a secretory or proliferative phenotype. This in turn might open up new avenues to the restoration of insulin secretion in people with type 2 diabetes. Of the many common genetic variants associated with type 2 diabetes, that in TCF7L2 remains the most studied because it has the greatest effect size. However, the mechanism by which this variant alters diabetes risk remains elusive. A new study adds another layer of complexity, suggesting that the effects of TCF7L2 are context-dependent, and highlights a novel interaction that might bias a β-cell to a secretory or proliferative phenotype. This in turn might open up new avenues to the restoration of insulin secretion in people with type 2 diabetes. Transcription factor-7–like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, β cell growth, and insulin secretionJournal of Biological ChemistryVol. 293Issue 36PreviewVariants in the transcription factor-7–like 2 (TCF7L2/TCF4) gene, involved in Wnt signaling, are associated with type 2 diabetes. Loss of Tcf7l2 selectively from the β cell in mice has previously been shown to cause glucose intolerance and to lower β cell mass. Deletion of the tumor suppressor liver kinase B1 (LKB1/STK11) leads to β cell hyperplasia and enhanced glucose-stimulated insulin secretion, providing a convenient genetic model for increased β cell growth and function. The aim of this study was to explore the possibility that Tcf7l2 may be required for the effects of Lkb1 deletion on insulin secretion in the mouse β cell. Full-Text PDF Open Access" @default.
• W2891879780 created "2018-09-27" @default.
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• W2891879780 date "2018-09-01" @default.
• W2891879780 modified "2023-10-17" @default.
• W2891879780 title "Walking a fine line between β-cell secretion and proliferation" @default.
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• W2891879780 doi "https://doi.org/10.1074/jbc.h118.005121" @default.
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