Cerebral function in diabetes mellitus

Abstract

Diabetes mellitus is a common metabolic disorder associated with chronic complications such as nephropathy, angiopathy, retinopathy and peripheral neuropathy. Diabetes is not often considered to have deleterious effects on the brain. However, long-term diabetes results in a variety of subtle cerebral disorders, which occur more frequently than is commonly believed. Diabetic cerebral disorders have been demonstrated at a neurochemical, electrophysiological, structural and cognitive level; however, the pathogenesis is still not clear. Probably alterations in cerebral blood supply and metabolic derangements play a role, as they do in the pathogenesis of diabetic neuropathy. Furthermore, the brain is also affected by recurrent episodes of hypoglycaemia and poor metabolic control. We describe herein the cerebral manifestations of diabetes and discuss the putative pathogenetic mechanisms.

Alteration of Interaction Between Astrocytes and Neurons in Different Stages of Diabetes: a Nuclear Magnetic Resonance Study Using [1-13C]Glucose and [2-13C]Acetate

“…Studies using magnetic resonance imaging techniques have identified abnormal white matter structure and function as well as reduced gray matter volume and density in diabetic patients [8,9]. All these abnormalities are closely related to brain metabolic disorders [10]. For example, decreased N-acetyl aspartate (NAA) [11] and increased myo-inositol (m-Ins) [12] concentrations have been observed in the white matter of individuals with diabetes by using localized proton nuclear magnetic resonance ( 1 H NMR).…”

“…Decreased glutamine (Gln) supply to gamma-aminobutyric acid (GABA)ergic neurons has been observed in the cortex and subcortex of young epileptic rats, whereas astrocytic metabolism has been increased in adult epileptic rats [22]. Mason et al applied [2][3][4][5][6][7][8][9][10][11][12][13] C]acetate as a tracer to evaluate the hypothesis that patients with type 1 diabetes exhibit increased blood-brain transport and monocarboxylic acid (MCA) metabolism to sustain upregulated MCA transporters during hypoglycemia [23]. 13 C MRS is a primary technique for studying brain metabolism.…”

Regulation of Structural Plasticity and Neurogenesis during Stress and Diabetes; Protective Effects of Glucocorticoid Receptor Antagonists

“…Nondiabetic control mice preferred the exploration of the object placed in a novel location while the diabetic mice did not, indicating impaired spatial object-placement memory. This mild disturbance is typically observed at early stages of diabetes, while during a more prolonged disease state more severe behavioral deficits were established [76,77].…”

“…Hence, remodeling of the structure of the hippocampus is accelerated and its vulnerability to cognitive dysfunctions is enhanced during diabetes in a process that can be blocked by antiglucocorticoid therapy. Previously, hyperglycemia and insulin deficiency were thought to underlie the hippocampal deficits (see [76,77] for reviews), but these possibilities can be excluded in view of the experiments of Revsin et al [75,78], although synergy between these conditions and the deleterious effect of hypercortisolemia cannot be ruled out. A rationale behind this observation is that the blockade of the GR would allow a more prominent function of neuroprotective MR-mediated actions [9].…”

“…Nondiabetic control mice preferred the exploration of the object placed in a novel location while the diabetic mice did not, indicating impaired spatial object-placement memory. This mild disturbance is typically observed at early stages of diabetes, while during a more prolonged disease state more severe behavioral deficits were established [76,77].While seeking to clarify the role of hypercorticism in the hippocampus of STZ•-diabetic mice, Revsin discovered that the GR antagonist mifepristone admin-Q8 istered for four consecutive days (from day 6 to 10 after onset of diabetes in the STZ model) partly prevented and/or reversed hippocampal functional deficits and morphological abnormalities [75]. The antagonist prevented astrogliosis and excessive neuronal activation and reversed the suppressed markers for neurogenesis in the hippocampus induced by the diabetic state and associated high corticosterone [66,75].…”