title: The brain in diabetes: molecular changes in neurons and their implications for end-organ damage.
abstract: Although secondary end-organ damage in diabetes has generally been thought to result from long-term passive shunting of excess glucose through alternative metabolic pathways, recent studies have elucidated a second mechanism of pathogenesis that involves active changes in gene expression in neurons of the CNS. These changes in gene expression result in molecular and functional changes that can become maladaptive over time. In this review, we examine two neuronal populations in the brain that have been studied in human beings and animal models of diabetes. First, we discuss overactivation of magnocellular neurosecretory cells within the hypothalamus and how it relates to the development of diabetic nephropathy. And second, we describe how changes in hippocampal synaptic plasticity can lead to cognitive and behavioural deficits in chronic diabetes. Changes in neuronal gene expression in diabetes represent a new pathway for diabetic pathogenesis. This pathway may hold clues for the development of therapies that, via the targeting of neurons, can slow or prevent the development of diabetic end-organ damage.
authors.affiliation: Department of Neurology and PVA/EPVA Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven 06510, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Klein
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000209:etiology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000209:etiology; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007031:Hypothalamus / Q000473:pathology / Q000502:physiology; D009473:Neuronal Plasticity; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism
chemical_list: D014667:Vasopressins