Insulin open-loop

The closed-loop type artificial pancreas (specifically 8-cell), which consists of an automatic continuous monitor of blood glucose level (BGL) and an automatic injector of insulin which are coupled with feed-back system, has great potential for prevention of diabetic complication such as micro-angiopathies(l). A large-scale closed-loop type artificial pancreas for bedside use has already been developed and is clinically used at some laboratories and hospitals (2-4). However, this device is limited to only bedside use. On the other hand, the open-loop type artificial pancreas which consists of only a insulin injecting pump without an automatic continuous monitor of BGL, has been developed and is going to be clinically used(5-7). This system, however, can not completely control BGL as well as the bare pancreas in a normal body and often causes lower BGL(8-9). 

Open-loop control systems are characterized by operation at two levels basal delivery up to and following the absorption of meals, and augmented delivery for short periods associated with the absorption of meals adjusted to the insulin requirement of the respective meal. Augmented flow rates have ranged from 4 X basal (5) to 15 x basal (6,7), and augmented periods have varied from a single bolus injection/meal in humans (8) to 7 h/day in dogs (9). 

The characteristics and limitations of these devices recently were reviewed (4), and were the subject of a recent symposium (10). Subsequent to this review, other researchers have reported their success using open-loop insulin delivery systems to maintain normoglycemia in dogs (7,9) and in humans (8,11-14). The effects of this restoration of normoglycemia on diabetic metabolism and blood chemistry are beginning to be reported (15-19), but no clear evidence of long-term beneficial effects of normoglycemia have yet been obtained. 

Unlike the bedside or portable insulin delivery systems for which commercially available peristaltic or syringe pumps may be used, the key component of an implantable (open-loop) artificial pancreas is the specially developed miniature insulin pump. 

A number of concerns regarding open-loop delivery of insulin in general, and delivery of insulin by the controlled-release micropump, in particular, remain to be resolved. The optimum site of insulin delivery (intravenous... 

With this device, diabetologists and biomedical researchers will be able to examine the relationship between safe and reliable metabolic control and the incidence of degenerative complications, and to assess the potential benefits to be derived from open-loop insulin delivery systems. 

All of the systems mentioned below are open-loop systems that is, an amount of insulin is administered, or insulin is delivered at a given rate, and for several hours this insulin manages the serum glucose in an unknown way. After some time, the glucose may or may not be measured, and another dose of insulin is administered, or the delivery rate is adjusted. 

Figure 23.11 Open-loop response of the patient s blood glucose to a constant infusion rate of 15 mU/min from her insulin pump.

Another group solved the crystal structure of the IGF-I RTK domain phosphorylated at two tyrosine residues within the activation loop and bound to an ATP analog. The ligand is not in a conformation compatible with phosphoryl transfer, and the activation loop is partially disordered. IGF-I RTK is trapped in a half-closed, previously unobserved conformation. This conformation may be intermediary between the open, inactive conformation and closed, active conformation of insulin and IGF-I RTKs. 

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