Dual self-regulated delivery of insulin and glucagon by a hybrid patch.
Ze-Jun WangJinqiang WangHongjun LiJicheng YuGuojun ChenAnna R KahkoskaValerie WuYi ZengDi WenJayson R MiedemaJohn B BuseZhen GuPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
Reduced β-cell function and insulin deficiency are hallmarks of diabetes mellitus, which is often accompanied by the malfunction of glucagon-secreting α-cells. While insulin therapy has been developed to treat insulin deficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains inadequate. Here, we describe a transdermal patch that mimics the inherent counterregulatory effects of β-cells and α-cells for blood glucose management by dynamically releasing insulin or glucagon. The two modules share a copolymerized matrix but comprise different ratios of the key monomers to be "dually responsive" to both hyper- and hypoglycemic conditions. In a type 1 diabetic mouse model, the hybrid patch effectively controls hyperglycemia while minimizing the occurrence of hypoglycemia in the setting of insulin therapy with simulated delayed meal or insulin overdose.
Keyphrases
- type diabetes
- glycemic control
- blood glucose
- induced apoptosis
- cell cycle arrest
- mouse model
- stem cells
- risk assessment
- cell death
- cell proliferation
- weight loss
- endoplasmic reticulum stress
- transcription factor
- oxidative stress
- respiratory failure
- blood pressure
- intensive care unit
- metabolic syndrome
- adipose tissue
- replacement therapy