Anti‐diabetic and neuroprotective effects of pancreatic islet transplantation into the central nervous system

Abstract

During the last decades, the central nervous system (CNS) was intensively tested as a site for islet transplantation in different animal models of diabetes. Immunoprivilege properties of intracranial and intrathecal sites were found to delay and reduce rejection of transplanted allo-islets and xeno-islets, especially in the form of dispersed single cells. Insulin released from islets grafted in CNS was shown to cross the blood-brain barrier and to act as a regulator of peripheral glucose metabolism. In diabetic animals, sufficient nutrition and oxygen supply to islets grafted in the CNS provide adequate insulin response to increase glucose level resulting in rapid normoglycemia. In addition to insulin, pancreatic islets produce and secrete several other hormones, as well as neurotrophic and angiogenic factors with potential neuroprotective properties. Recent experimental studies and clinical trials provide a strong support for delivery of islet-derived macromolecules to CNS as a promising strategy to treat various brain disorders. This review article focuses mainly on analysis of current status of intracranial and intrathecal islet transplantations for treatment of experimental diabetes and discusses the possible neuroprotective properties of grafted islets into CNS as a novel therapeutic approach to brain disorders with cognitive dysfunctions characterized by impaired brain insulin signalling. Copyright © 2015 John Wiley & Sons, Ltd.

The role of short-chain fatty acids in microbiota–gut–brain communication

“…Insulin is also a CNS regulatory peptide, and peripheral insulin is taken up by the brain but the mechanisms remains a matter of debate 139 . Insulin may influence the brain from the periphery, following intravenous administration, or centrally, following intranasal and intracereboventricular routes to the CNS 139 or intracranial or intrathecal transplantation of pancreatic islets 140 . A large body of literature suggests that insulin availability and/or alterations in insulin receptor sensitivity/availability is relevant to brain function.…”

Insulin delivery to the brain using intracranial implantation of alginate-encapsulated pancreatic islets

“…Another obstacle for successful islet transplantation is the immune rejection of allo‐ or xeno‐grafts, even when islets are transplanted in such immuno‐privileged site as the CNS (Lazard et al, ). One of the most promising approaches to protect grafted islets without using immunosuppressive drugs is by means of encapsulation technologies that create a physical barrier to provide immune protection.…”

“…glucose level). During the last decades the central nervous system (CNS) was intensively tested as a site for pancreatic islet transplantation in different animal models of diabetes (Lazard et al, ). Insulin released from islets grafted in the brain was shown to cross the blood–brain barrier and act as a regulator of peripheral glucose metabolism.…”

Comment on Gray et al. Insulin Regulates Brain Function, but How Does It Get There? Diabetes 2014;63:3992–3997

“…In addition, islets secrete other pancreatic hormones (e.g., glucagon, somatostatin, amylin) and various neurotrophic factors that play an important role in neuroprotection. Insulin and other hormones derived from grafted islets cross the blood-brain barrier and reach the peripheral targets (liver, muscle, and adipose tissues) participating in regulation of glucose homeostasis (2).…”

“…Recently, we suggested that pancreatic islets intracranially grafted into the rat subarachnoid space may serve as a promising tool for insulin delivery to the brain for treatment of cognitive dysfunctions (2,3). To test this hypothesis, islets were grafted into the subarachnoid space around the olfactory bulb and prefrontal cortex of rats displaying schizophrenia-like behavioral dysfunctions induced by exposure to dizocilpine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor.…”