Reinnervation of Pancreatic Islets and Regulation of Insulin Secretion by Hepatic Sympathetic Nerves after Intraportal Transplantation of Islets into Livers of Diabetic Rats

Abstract

It was the aim of this study to elucidate whether intraportally transplanted pancreatic islets were reinnervated after transplantation and whether the secretion of insulin from pancreatic islets might be modulated by the vegetative innervation of recipient livers. Two weeks after intraportal transplantation of 2000 neonatal pancreatic islets recipient rats completely recovered from streptozotocin-induced diabetes. Predominantly catecholaminergic, but also cholinergic nerve fibers were detected in islet cell complexes between beta-cells. Corresponding electron micrographs showed beta-cells in close contact with axons of nonmyelinated nerve fibers. Perfusion studies with livers of recipient rats revealed that the inhibition by hepatic sympathetic nerves of insulin secretion was mediated via alpha 2-receptors as in normal pancreatic islets.

Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site

“…43,44 Correlation was shown between the success rate for diabetes reversal and the minimal number of syngeneic islets: 100% reversal with 1000 islets (approximately 3500 islets/ kg), 33% with 700 islets (2500 islets/kg), and 0% with 500 islets (1700 islets/kg). In the 1990s, 2000 syngeneic islets were reported to reverse diabetes in LEW rats.…”

“…In the 1990s, 2000 syngeneic islets were reported to reverse diabetes in LEW rats. 43,44 Correlation was shown between the success rate for diabetes reversal and the minimal number of syngeneic islets: 100% reversal with 1000 islets (approximately 3500 islets/ kg), 33% with 700 islets (2500 islets/kg), and 0% with 500 islets (1700 islets/kg). 45 Another study reported 0% reversal with 2500 islets/kg.…”

Functional stimulation of graft nerves has minor effects on insulin release from transplanted rat pancreatic islets

“…This is in contrast to some previous experiments where physical exercise induced a decrease in serum insulin concentration from islets implanted into the liver in rats, also after adrenalectomy ( 22,23 ). Also direct stimulation of hepatic nerves in the perfused liver of rats transplanted intraportally with neonatal islets demonstrated an inhibition of insulin release 9 months post-transplantation ( 24 ), presumably through α 2 -adrenoceptors ( 25 ). Islets implanted into the portal vein also exhibit pulsatile insulin secretion, which is likely to be due to reinnervation ( 26-28 ).…”

Simulated Cholinergic Reinnervation ofβ(INS-1) Cells: Antidiabetic Utility of Heterotypic Pseudoislets ContainingβCell and Cholinergic Cell

“…Under physiological conditions, insulin secretion is controlled by the sympathetic and parasympathetic nervous systems. When the sympathetic nerve is stimulated, it releases norepinephrine, which inhibits insulin secretion by inducing vasoconstriction and suppressing β cell function [ 6 ]. In contrast, when the parasympathetic nerve is stimulated, it can promote insulin secretion by releasing acetylcholine, which activates muscarinic receptors in β cells [ 7 ].…”