Factors influencing insulin secretion from encapsulated islets.
Adequate regulation of glucose levels by a microencapsulated pancreatic islet graft requires a minute-to-minute regulation of blood glucose. To design such a transplant, it is mandatory to have sufficient insight in factors influencing the kinetics of insulin secretion by encapsulated islets. The present study investigates factors influencing the glucose-induced insulin response of encapsulated islets in vitro. We applied static incubations and did the following observations. (i) Small islets (90-120 microm) showed a similar instead of a lower glucose-induced insulin response, suggesting that inclusion of only small islets, which are associated with lower protrusion and failing rates, has no consequences for the functional performance of the graft. (ii) A capsule diameter of 800 microm showed identical rather than lower glucose-induced insulin responses as smaller, 500-microm capsules. (iii) Capsule membranes constructed with a conventional permeability interfered with diffusion of insulin, as illustrated by a lower response of islets in capsules with a 10-min poly-L-lysine (PLL) membrane than islets in capsules with a 5-min PLL membrane. (iv) Irrespective of the tested porosity, the capsules provided sufficient immunoprotection because the 10-min PLL membranes did block diffusion of the cytokines IL-1beta (17 kDa) and TNF-alpha (70 kDa) while the 5-min PLL membranes interfered with the diffusion of the vast majority of the cytokines. We conclude that capsules containing small islets (90-120 microm) and a membrane with a lower permeability than routinely applied is preferred in order to obtain a graft with adequate glucose-induced insulin responses.
Immunoendocrinology, Department of Pathology and Laboratory Medicine, Section of Medical Biology, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. B.J.DE.HAAN@MED.RUG.NL
Bart J
BJ
de Haan
Marijke M
MM
Faas
Paul
P
de Vos
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002214:Capsules / Q000592:standards / Q000627:therapeutic use; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000493:pharmacokinetics; D004058:Diffusion / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D007700:Kinetics; D008297:Male; D008567:Membranes, Artificial; D051381:Rats; D011919:Rats, Inbred Strains; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D002214:Capsules; D016207:Cytokines; D007328:Insulin; D008567:Membranes, Artificial; D005947:Glucose