Related Experiment Video
Updated: May 18, 2026
10:09
Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets
Published on: May 11, 2015
Evaluating insulin secretagogues in a humanized mouse model with functional human islets.
Jian Luo1, Kathy Nguyen, Michael Chen
1NGM Biopharmaceuticals, Inc., South San Francisco, CA 94080, USA. jluo@ngmbio.com
Metabolism: Clinical and Experimental
|September 18, 2012
Summary
A novel humanized mouse model successfully supports human islet grafts, enabling effective evaluation of insulin secretagogues. This model accurately predicts how drugs like GLP-1 and GPR40 agonists impact human beta cell function and glucose control.
Area of Science:
- Endocrinology and Metabolism
- Transplantation Biology
- Pharmacology
Background:
- Developing clinically relevant in vivo models for evaluating therapeutic agents targeting human islets is crucial.
- Existing models often lack the specificity to accurately assess novel insulin secretagogues on human beta cells.
Purpose of the Study:
- To establish a rapid, easy, and clinically relevant in vivo model for testing insulin secretagogues using functional human islets in a humanized mouse model.
- To investigate the efficacy of various insulin secretagogues in this novel humanized mouse model.
Main Methods:
- Human islets were transplanted into the kidney capsule of immunodeficient, streptozotocin-induced diabetic mice.
- Graft function was monitored via blood glucose levels, followed by physiological and pharmacological characterization.
- The model was tested with clinically used insulin secretagogues (GLP-1 receptor agonists, sulfonylureas, meglitinides, DPP-4 inhibitors) and GPR40 agonists.
Main Results:
- Successful long-term survival of human islet grafts was achieved in immunodeficient mice.
- Oral glucose challenge elicited a robust human C-peptide response, distinct from mouse C-peptide.
- Tested insulin secretagogues, including GLP-1, exenatide, glyburide, nateglinide, sitagliptin, and GPR40 agonists, effectively stimulated human C-peptide secretion and improved glucose control.
Conclusions:
- The developed humanized mouse model with human islet grafts accurately mimics in vivo human islet function.
- This model serves as a powerful platform for evaluating novel insulin secretagogues and other therapeutic agents targeting human beta cells.
