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TCF7L2 rs7903146 impairs islet function and morphology in non-diabetic individuals
O Le Bacquer1,2,3, J Kerr-Conte4,5, S Gargani1,2
1Université Lille Nord de France, Lille, France.
Diabetologia
|August 23, 2012
Summary
The TCF7L2 rs7903146 T allele impairs human islet function and morphology, reducing insulin secretion and islet number, impacting type 2 diabetes risk.
Area of Science:
- Endocrinology
- Genetics
- Diabetes Research
Background:
- Transcription factor 7-like 2 (TCF7L2) is linked to type 2 diabetes risk via genetic polymorphisms.
- The specific impact of the TCF7L2 rs7903146 T allele on human pancreatic islet biology remains unclear.
Purpose of the Study:
- To investigate the functional and morphological effects of the TCF7L2 rs7903146 T allele on human pancreatic islets.
- To correlate TCF7L2 genotype with islet function and morphology in individuals without diabetes.
Main Methods:
- Genotyping of the TCF7L2 rs7903146 variant in pancreatic tissue from 187 brain-deceased donors (HbA1c <6.5%).
- Immunostaining for glucagon and C-peptide to assess alpha and beta cell subpopulations and islet morphology.
- In vitro assessment of isolated islet function, correlating genotype with insulin secretion.
Main Results:
- The TCF7L2 rs7903146 (T/T) genotype was associated with reduced basal and glucose-stimulated insulin secretion.
- Islet density was reduced, while islet size was increased in T/T carriers.
- An increased glucagon/C-peptide ratio was observed, particularly in larger islets.
Conclusions:
- The TCF7L2 rs7903146 risk allele is linked to impaired insulin secretion and altered human islet number and morphology.
- These findings highlight TCF7L2's role in modulating islet function and morphology, potentially informing type 2 diabetes therapeutics.
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