Related Experiment Video
Updated: Jan 7, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
A synthetic hyperglycemia-sensing gene circuit enhances blood glucose homeostasis in diabetic mice
Yuan Zhang1, Shuai Deng2, Yanlun Zhu2
1Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People's Republic of China.
Abstract:
Synthetic gene circuits can be programmed to produce therapeutic proteins in response to the presence of disease biomarkers. Here, we established a hyperglycemia-sensing gene circuit to enhance blood glucose homeostasis in diabetic mouse models. To achieve such a sensing mechanism, we functionally linked the O-GlcNAcylation-mediated nuclear translocation of Yes-associated protein (YAP), a universally existing cellular pathway, to a prokaryotic Tet-Off transcription regulatory system. This linkage involved engineering two chimeric transcription factors that promote intense transcription activity in response to supraphysiological glucose levels to induce the expression of therapeutic proteins from the Tet-inducible promoter. In vivo application of the gene circuit enhanced blood glucose homeostasis in diabetic mouse models by coordinating hyperglycemia-triggered insulin or glucagon-like peptide-1 (GLP-1) expression and ameliorated hyperglycemia-induced tissue damage in type 1 and type 2 diabetic mice. Besides its antidiabetic therapeutic potential, the hyperglycemia-sensing gene circuit demonstrates the generalized possibility of repurposing widely evolved sensors from various organisms for customized therapeutics.
More Related Videos
16:59Neo-Islet Formation in Liver of Diabetic Mice by Helper-dependent Adenoviral Vector-Mediated Gene Transfer
Published on: October 10, 2012
07:35Author Spotlight: Investigating the Blood Glucose Homeostasis in Murine Brain Using a Cost-Effective Hyperglycemic And Hypoglycemic Clamp Technique
Published on: January 26, 2024
Related Concept Videos
Glucose Homeostasis: Regulation of Blood Glucose
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Hypoglycemia and Glucagon
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...
Cell Specific Gene Expression
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...