Cơ chế phân tử và tế bào của metformin: một cái nhìn tổng quan
Tóm tắt
Trong hơn 50 năm qua, đã có nhiều nỗ lực nhằm hiểu rõ hơn về các cơ chế phân tử và tế bào của metformin, một hoạt chất chống tăng đường huyết mạnh, hiện đang được khuyến cáo là liệu pháp điều trị đường uống hàng đầu cho bệnh tiểu đường loại 2 (T2D). Tác dụng chính của thuốc này từ nhóm biguanide là giảm đáng kể sản xuất glucose ở gan, chủ yếu thông qua việc ức chế tạm thời nhẹ nhàng chuỗi hô hấp ty thể phức hợp I. Ngoài ra, sự giảm năng lượng ở gan dẫn đến việc kích hoạt AMPK (protein kinase gắn với AMP), một cảm biến trao đổi chất tế bào, cung cấp một cơ chế được chấp nhận rộng rãi cho tác động của metformin lên quá trình gluconeogenesis ở gan. Việc chứng minh rằng phức hợp hô hấp ty thể I, nhưng không phải AMPK, là mục tiêu chính của metformin đã được củng cố gần đây thông qua việc cho thấy hiệu ứng chuyển hóa của thuốc được bảo tồn trong chuột thiếu AMPK đặc hiệu ở gan. Ngoài tác động đến chuyển hóa glucose, metformin đã được báo cáo là khôi phục chức năng buồng trứng ở hội chứng ovarium đa nang (PCOS), giảm gan nhiễm mỡ và giảm các biến chứng vi mạch và đại mạch liên quan đến T2D. Việc sử dụng metformin cũng đã được đề xuất gần đây như một phương pháp điều trị hỗ trợ cho ung thư hoặc tiểu đường thai kỳ và cho việc phòng ngừa trong các quần thể tiền tiểu đường. Những lĩnh vực điều trị mới nổi này của metformin sẽ được xem xét cùng với những phát hiện gần đây từ các nghiên cứu dược di truyền liên kết các biến thể di truyền với phản ứng thuốc, một bước tiến hứa hẹn hướng tới y học cá thể hóa trong điều trị T2D.
Từ khóa
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