Neurodegenerative disorders associated with diabetes mellitus

Abstract

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes

“…The reactive α-keto-aldehyde MG is the most important carbonyl, formed endogenously as a byproduct of the glycolytic pathway and formed either by the degradation of triosephosphates, or non-enzymatically by sugar fragmentation reactions (5). MG is gradually accumulated under hyperglycemic conditions, which may induce oxidative stress (6).…”

Mitochondrial dysfunction in pancreatic β-cells in Type 2 Diabetes

“…Not only do these patients develop a fatal neurological disorder, about one third of the patients also exhibits diabetes (Ristow, 2004). Moreover, several studies have shown linkage of Type 2 Diabetes with the locus containing the FRDA gene (9q13) (Lindgren et al, 2002).…”

Neuroprotective effects of geniposide on Alzheimer’s disease pathology

“…In the present review, we explore a possibility to develop a new strategy to treat AD using receptor agonists of GLP-1R and explain the possible molecular mechanism. Epidemiological studies found a correlation between an increased risk of developing AD and T2DM (Ristow, 2004;Biessels et al, 2006;Haan, 2006). Further research showed a range of shared pathophysiological changes seen in T2DM and AD (Akter et al, 2011).…”