Sự tham gia của con đường tín hiệu Wnt và TCF7L2 trong bệnh tiểu đường: Hiểu biết hiện tại, tranh cãi và góc nhìn

Wilfred Ip1, Yu-Ting Chiang2, Tianru Jin2
1Institute of Medical Science, University of Toronto, Toronto, Canada
2Department of Physiology, University of Toronto, Toronto, Canada

Tóm tắt

tóm tắt

Con đường tín hiệu Wnt được phát hiện ban đầu do vai trò của nó trong gây ung thư và sự phát triển của Drosophila và các sinh vật nhân thực khác. Yếu tố hiệu ứng chính của con đường này, yếu tố phiên mã lưỡng phần β-cat/TCF, được hình thành từ β-catenin tự do (β-cat) và một protein TCF, bao gồm TCF7L2. Những nghiên cứu gần đây đã chỉ ra vai trò của con đường tín hiệu Wnt trong điều hòa chuyển hóa và sự liên quan của nó đối với bệnh tiểu đường và các bệnh chuyển hóa khác. Các nghiên cứu liên kết toàn bộ genome đã cho thấy rằng nhiều thành phần chính của con đường tín hiệu Wnt có liên quan đến điều hòa chuyển hóa và sự phát triển của bệnh tiểu đường tuýp 2 (T2D). Mặc dù có những quan sát gây tranh cãi liên quan đến vai trò của tín hiệu Wnt trong sự phát triển và chức năng của các tiểu đảo tụy, nhưng sự phát hiện của mối liên hệ giữa một số đa hình nucleotide đơn lẻ của TCF7L2 và khả năng mắc T2D đã thúc đẩy những nỗ lực lớn trong việc khám phá vai trò của tín hiệu Wnt trong chức năng của các tế bào β tụy và điều hòa glucose. Chúng tôi đã giới thiệu sự hiểu biết cơ bản của chúng tôi về con đường tín hiệu Wnt kinh điển, tóm tắt kiến thức hiện tại của chúng tôi về mối liên quan của nó trong điều hòa chuyển hóa và T2D, thảo luận về công trình nghiên cứu TCF7L2 như một gen nhạy cảm với T2D, và trình bày vai trò gây tranh cãi của tín hiệu Wnt và TCF7L2 trong các tiểu đảo tụy cũng như chức năng chuyển hóa tiềm năng của chúng trong các cơ quan khác. Chúng tôi mở rộng cái nhìn của chúng tôi về sự giao thoa giữa tín hiệu Wnt, insulin và chuỗi tín hiệu FOXO, điều này làm sáng tỏ thêm sự phức tạp của con đường tín hiệu Wnt trong điều hòa chuyển hóa. Cuối cùng, chúng tôi đã trình bày quan điểm của chúng tôi.

Từ khóa


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