Beta cells are important for islet innervation: evidence from purified rat islet-cell grafts

Pancreatic islets receive an extensive and complex innervation that includes sympathetic, noradrenergic nerve fibres also storing neuropeptide Y. Islets transplanted to the kidney capsule become progressively reinnervated, mainly by sympathetic fibres and to a lesser extent by parasympathetic and sensory fibres. The density of nerve fibres in the islet grafts is often higher than in the graft-bearing organ, suggesting that the grafted islets contain factors that promote ingrowth of nerve fibres. To find out if beta cells are of any importance for attracting nerve fibres, purified preparations of rat islet beta and non-beta cells were transplanted to the kidneys of nude mice. Some of the mice were rendered diabetic by alloxan injection before transplantation. Immunocytochemical analysis revealed that the beta-cell grafts became richly reinnervated by noradrenergic (tyrosine hydroxylase-containing) nerve fibres, also storing neuropeptide Y. Non-beta islet-cell grafts were virtually devoid of demonstrable nerve fibres. There was no discernible difference in the reinnervation pattern between diabetic and non-diabetic mice. The findings indicate that factors mediating islet neurotrophism are produced by the beta cells.