Vai trò của các adipokine trong viêm cơ xương và độ nhạy insulin

Springer Science and Business Media LLC - Tập 15 - Trang 1-11 - 2018
Thomas Nicholson1, Chris Church2, David J. Baker2, Simon W. Jones1,3
1MRC-ARUK Centre for Musculoskeletal Ageing Research, Medical School, Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK
2MedImmune, Cardiovascular and Metabolic Disease (CVMD), Cambridge, UK
3Institute of Inflammation and Ageing, MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Queen Elizabeth Hospital, Birmingham, UK

Tóm tắt

Hiện nay có một nhu cầu lâm sàng chưa được đáp ứng về việc phát triển các liệu pháp dược lý tốt hơn nhằm cải thiện khả năng xử lý glucose ở bệnh nhân tiểu đường loại II có thừa cân. Để đạt được điều này, việc xác định tác động của các adipokine liên quan đến béo phì đối với độ nhạy insulin của cơ xương đã nổi lên như một lĩnh vực quan trọng trong nghiên cứu khám phá thuốc. Bài tổng quan này tập hợp dữ liệu về vai trò chức năng của các adipokine đối với tín hiệu insulin tại cơ xương, làm nổi bật một số adipokine mới chưa được nghiên cứu nhiều và cung cấp cái nhìn về hướng nghiên cứu trong tương lai. Các adipokine như leptin, resistin, visfatin và adiponectin đã được chứng minh là ảnh hưởng đến độ nhạy insulin của cơ xương bằng cách tác động vào hoạt động của các thành phần trong các con đường tín hiệu insulin, ảnh hưởng đến sự chuyển vị GLUT4 và điều chỉnh quá trình tiếp nhận glucose ở cơ xương do insulin. Hơn nữa, phân tích proteomics của hệ thống bài tiết mô mỡ gần đây đã xác định một số adipokine mới bao gồm vaspin, chemerin và pref-1 có liên quan đến béo phì và kháng insulin ở người và ảnh hưởng chức năng lên các con đường tín hiệu insulin. Tuy nhiên, chủ yếu, các phát hiện chức năng này là kết quả của các nghiên cứu trên chuột, với các nghiên cứu in vitro sử dụng mô hình bào tương L6 của chuột hoặc bào tương C2C12 và/hoặc các ống cơ. Mặc dù đã có phương pháp để tách biệt và nuôi cấy các bào tương người và đồng hóa chúng thành các ống cơ, nhưng việc sử dụng mô hình mô cơ người trong nghiên cứu in vitro để xác thực chức năng của các adipokine đối với độ nhạy insulin của cơ xương còn hạn chế. Hiểu rõ cơ chế hoạt động và chức năng của các adipokine trong việc trung gian độ nhạy insulin ở cơ xương có thể dẫn đến việc phát triển các liệu pháp mới cho bệnh nhân tiểu đường loại 2. Tuy nhiên, cho đến nay, các nghiên cứu được thực hiện trên tế bào và mô cơ người còn hạn chế. Những nghiên cứu in vitro trên con người này nên được ưu tiên để giảm thiểu rủi ro thất bại của các loại thuốc ứng viên trong lâm sàng do giả định rằng các nghiên cứu xác thực mục tiêu cơ xương trên chuột sẽ có thể chuyển giao sang người.

Từ khóa

#adipokine #độ nhạy insulin #cơ xương #viêm cơ #tiểu đường loại II #béo phì #nghiên cứu dược lý

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