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Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling
Essam Refai1, Nancy Dekki, Shao-Nian Yang
1Department of Medical Biochemistry and Biophysics, The Rolf Luft Center for Diabetes Research, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Summary
Transthyretin tetramer enhances pancreatic beta-cell function by promoting insulin release and protecting against apoptosis. Lower tetramer levels in type 1 diabetes suggest its conversion to monomer may contribute to beta-cell failure.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Transthyretin (TTR) is a serum transport protein primarily existing as a tetramer.
- Its role in pancreatic beta-cell function was previously unknown.
Purpose of the Study:
- To investigate the role of TTR tetramer in pancreatic beta-cell stimulus-secretion coupling.
- To determine TTR's effect on insulin release, beta-cell electrical activity, and apoptosis.
- To examine TTR levels in patients with type 1 diabetes.
Main Methods:
- Studied the effect of TTR tetramer on glucose-induced insulin secretion and intracellular calcium ([Ca(2+)](i)) in beta-cells.
- Assessed TTR's impact on beta-cell electrical activity and voltage-gated calcium channels.
- Analyzed TTR tetramer and monomer concentrations in sera from type 1 diabetes patients.
Main Results:
- TTR tetramer significantly promoted glucose-induced insulin release and increased [Ca(2+)](i).
- TTR tetramer directly influenced glucose-induced electrical activity and calcium channel function.
- TTR tetramer demonstrated protective effects against beta-cell apoptosis.
- Type 1 diabetes patients showed decreased TTR tetramer and increased monomer levels in their sera.
Conclusions:
- TTR tetramer is a crucial component of normal pancreatic beta-cell function.
- The conversion of TTR tetramer to monomer may play a role in beta-cell dysfunction and destruction observed in type 1 diabetes.