Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood, and by a disappearance of polyuria and polydipsia. The reversal remained stable for at least 9 months. This study determined whether intraportally transplanted pancreatic islets were reinnervated after transplantation and whether the secretion of insulin and glucagon from pancreatic islets might be modulated by the vegetative innervation of recipient livers. Predominantly catecholaminergic but also cholinergic nerve fibers were detected not only within the portal tracts around hepatic arteries, portal veins, and bile ducts, but also at the borderline of hepatocytes and β-cells and in islet cell complexes between β-cells. Corresponding electron micrographs showed β-cells in close contact with axons of nonmyelinated nerve fibers. Isolated livers were single pass perfused via both the hepatic artery and the portal vein. An increase in glucose level from 5 to 14 mmoW enhanced hepatic glucose uptake and increased insulin secretion from transplanted islets with a biphasic secretion profile but had no effect on glucagon output. Stimulation of the nerve plexus around the hepatic artery and the portal vein (7.5 Hz, 2 min), which activates primarily the sympathetic system, not only reduced glucose uptake and perfusion flow but also completely reversed the glucose-stimulated increase in insulin secretion. Nerve stimulation did not influence glucagon secretion. The α1-aradrenergic antagonist prazosin and the β-blocker propranolol completely blocked the nerve stimulation-dependent alterations in glucose balance and in perfusion flow but did not affect the reversal of the glucose-stimulated increase in insulin release caused by nerve stimulation. This indicates indirectly that the inhibition by sympathetic liver nerves of insulin secretion was mediated via α2-receptors as in normal pancreatic islets. Experiments with the α2-adrenergic antagonist yohimbine were in line with this conclusion.
Intraportal Transplantation of Pancreatic Islets Into Livers of Diabetic Rats: Reinnervation of Islets and Regulation of Insulin Secretion by the Hepatic Sympathetic Nerves
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Andreas Gardemann, Kurt Jungermann, Volker Groβe, Lothar Cossel, Frank Wohlrab, Hans Jürgen Halm, Wolfgang Blech, Wolfgang Hildebrandt; Intraportal Transplantation of Pancreatic Islets Into Livers of Diabetic Rats: Reinnervation of Islets and Regulation of Insulin Secretion by the Hepatic Sympathetic Nerves. Diabetes 1 November 1994; 43 (11): 1345–1352. https://doi.org/10.2337/diab.43.11.1345
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