Insulin-glucose feedback regulation

If the oscillations derive from an instability in the insulin-glucose feedback regulation, where do we find the delay that can produce such an instability ... 

We would like to acknowledge many years of fruitful collaboration with Jeppe Sturis and Kenneth Polonsky in the area of insulin-glucose feedback regulation. Christian Binder provided the clinical results applied in our analysis of insulin absorption from subcutus. Brian Lading, Yuri Maistrenko, and Sergiy Yanchuk contributed to our study of bifurcation and synchronization phenomena in pancreatic -cells. 

Fig. 27 Cross-sectional view of a bioresponsive insulin delivery system, a feedback-regulated drug delivery system, showing the glucose oxidase-entrapped hydrogel membrane constructed from amine-containing hydrophilic pol5mier. The mechanism of insulin release, in response to the influx of glucose, is also illustrated. (From Ref. l)...

Three hormones play a part in the regulation of carbohydrate metabolism epinephrine, glucagon, and insulin. Epinephrine acts on muscle tissue to raise levels of glucose on demand, while glucagon acts on the liver, also to increase the availability of glucose. Feedback control plays a role in the process and ensures that the amount of glucose made available does not reach an excessive level (Section 24.3). The role of insulin is to trigger the feedback response that achieves this further control. 

Figure 6.19 Regulation of the synthesis of glycogen from glucose in liver and muscle. Insulin is the major factor stimulating glycogen synthesis in muscle it increases glucose transport into the muscle and the activity of glycogen synthase, activity which is also activated by glucose 6-phosphate but inhibited by glycogen. The latter represents a feedback mechanism and the former a feedforward. The mechanism by which glycogen inhibits the activity is not known. The mechanism for the insulin effect is discussed in Chapter 12.

Regulation of insulin secretion is often described as a simple feedback loop between glucose and insulin. However, insulin is released by a number of biochemicals, and several hormones directly or indirectly influence insulin release. Moreover, the mode of release varies with the type of stimulus, and acute and delayed responses can be distinguished [133]. 

The factors that trigger hormonal release are many and varied, their nature depending on the hormone in question for example, adrenaline and noradrenaline are secreted in response to stimulation of the sympathetic system. Insulin is secreted in response to an increase in the blood sugar level, while glucagon is secreted when the level falls. A dual control system also operates with respect to the regulation of the level of Ca ions in blood. When this is lowered parathormone is secreted, while calcitonin is secreted when the level is raised. These systems both appear to operate on a simple negative feedback basis, and when the level of glucose or Ca ions in the blood has been restored to normal, the hormone levels are also restored. 

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