Diabetes mellitus has become a major social health problem affecting all of the world. The key to efficiently treating type Ⅰ and advanced type Ⅱ diabetes is to inject insulin with a precise dose according to the blood glucose levels (BGLs). Thus, smart insulin delivery systems responding to glucose concentration of the surroundings have attracted extensive interest these years. This review mainly focuses on chemically controlled closed-loop insulin delivery able to mimic pancreas activity. One of the greatest advantages of these systems is to regulate insulin dosage and delivery by BGLs on an automated and continuous basis. So called this feedback-controlled insulin delivery system ‘artificial pancreas’. Strategies to achieve this ‘artificial pancreas’ are through glucose-responsive insulin delivery systems, typically based on the glucose-sensing elements of glucose oxidase (GOx), glucose binding protein (GBP), or phenylboronic acid (PBA). Main mechanisms and most recent studies are discussed in this review.

Contents
1 Introduction
2 Glucose oxidase based system
2.1 Swelling/shrinking mechanisms
2.2 Disassembling/degradation mechanisms
3 Glucose binding proteins based system
4 Phenylboronic acid moieties based system
4.1 Swelling/shrinking mechanisms
4.2 Glucose replacement mechanisms
4.3 Disassembling/degradation mechanisms
4.4 Other mechanisms
5 Conclusion and outlook