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Updated: Jan 24, 2026

Glucose-Stimulated Insulin Secretion via Perfusion through the Mice Vasculature with an Intact Pancreas
Published on: July 25, 2025
Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia
Jinqiang Wang1,2, Jicheng Yu3, Yuqi Zhang3
1Department of Bioengineering, University of California, Los Angeles, CA 90095.
Abstract:
Insulin therapy in the setting of type 1 and advanced type 2 diabetes is complicated by increased risk of hypoglycemia. This potentially fatal complication could be mitigated by a glucose-responsive insulin analog. We report an insulin-facilitated glucose transporter (Glut) inhibitor conjugate, in which the insulin molecule is rendered glucose-responsive via conjugation to an inhibitor of Glut. The binding affinity of this insulin analog to endogenous Glut is modulated by plasma and tissue glucose levels. In hyperglycemic conditions (e.g., uncontrolled diabetes or the postprandial state), the in situ-generated insulin analog-Glut complex is driven to dissociate, freeing the insulin analog and glucose-accessible Glut to restore normoglycemia. Upon overdose, enhanced binding of insulin analog to Glut suppresses the glucose transport activity of Glut to attenuate further uptake of glucose. We demonstrate the ability of this insulin conjugate to regulate blood glucose levels within a normal range while mitigating the risk of hypoglycemia in a type 1 diabetic mouse model.
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