The islets must respond quickly to changes in glucose. A device or coating that will not allow islets to respond rapidly to changes in blood sugar will not cure diabetes. If the islets are far from the surface of the immunoisolation membrane, as for instance in a hollow fiber, many minutes may pass from normalization of blood glucose to normalization in the fluid immediately surrounding the islets. This can result in overshooting, leading to potentially dangerous hypoglycemia.
The cartoon shows the appearance of insulin following a glucose challenge. First, an islet releases a burst of insulin (first phase response) followed by steady secretion (second phase). When the glucose disappears, insulin secretion declines to baseline in a few minutes. Second, an islet in a small capsule produces a similar but somewhat blunted curve. Insulin must diffuse through the small capsules, but not far. In contrast the hollow fiber is so big that insulin diffusion takes many minutes, and the insulin curve takes over 30 minutes to return to baseline. Hollow fibers have been reported to cause hypoglycemia in animals.
The Islet Sheet responds quickly because of the small dimensions needed to allow oxygen diffusion. The thin sheet curve should be similar to the small capsules curve.