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Review
. 2024 Jan;39(1):3-17.
doi: 10.1007/s12291-022-01107-y. Epub 2022 Dec 16.

Diabetic Encephalopathy: Role of Oxidative and Nitrosative Factors in Type 2 Diabetes

Debashree Mazumdar  1 , Santosh Singh  1
Affiliations
Review

Diabetic Encephalopathy: Role of Oxidative and Nitrosative Factors in Type 2 Diabetes

Debashree Mazumdar et al. Indian J Clin Biochem. 2024 Jan.

Abstract

Diabetes mellitus is a set of complex metabolic disorders characterized by chronic hyperglycaemic condition due to defective insulin secretion (Type 1) and action (Type 2), which leads to serious micro and macro-vascular damage, inflammation, oxidative and nitrosative stress and a deranged energy homeostasis due to imbalance in the glucose and lipid metabolism. Moreover, patient with diabetes mellitus often showed the nervous system disorders known as diabetic encephalopathy. The precise pathological mechanism of diabetic encephalopathy by which it effects the central nervous system directly or indirectly causing the cognitive and motor impairment, is not completely understood. However, it has been speculated that like other extracerebellar tissues, oxidative and nitrosative stress may play significant role in the pathogenesis of diabetic encephalopathy. Therefore, the present review aimed to explain the possible association of the oxidative and nitrosative stress caused by the chronic hyperglycaemic condition with the central nervous system complications of the type 2 diabetes mellitus induced diabetic encephalopathy.

Keywords: Cognitive and motor impairment; Diabetes mellitus; Diabetic encephalopathy; Type 2 diabetes mellitus; Oxidative and nitrosative stress.

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Conflict of interest statement

Competing interestThe authors have no competing interests to declare that are relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Insulin signalling in peripheral tissues and CNS: The insulin signalling pathway tends to vary with respect to the IRS adaptor molecule in peripheral tissues and in brain. Signalling transduction is independent of IRS 1 molecule in the brain unlike of peripheral tissues. Further transduction of signal is similar for both extracerebral tissues and CNS
Fig. 2
Fig. 2
Insulin signalling impairment in peripheral tissues and CNS: Diabetes results in prolonged hyperglycaemic condition which results in glucose toxicity and hyperinsulinemia which downregulates the PI3K signalling pathway thus leading to an impaired insulin signalling and Insulin resistance in some cases
Fig. 3
Fig. 3
Hyperglycaemia and oxidative stress: Oxidative stress plays a key link between chronic hyperglycaemic condition and tissue damage. Reduced glucose uptake results due to the decrease in the translocation of GLUT 4 transporters which maintains the hyperglycaemic condition thus creating a continuous cycle of hyperglycaemia induced oxidative stress and vice versa
Fig. 4
Fig. 4
Hyperglycaemia and nitrosative stress: Hyperglycaemia induced nitrosative stress leads to a decline in eNOS derived NO which reduces GLUT 4 translocation causing Insulin resistance. However, increase in the hyperglycaemia induced iNOS derived NO leads to impaired insulin secretion as well as neuronal structural impairments
Fig. 5
Fig. 5
Diabetes induced neurological impairments: Neurocognitive and behavioural impairments vary in case of T1DM and T2DM depending on the nature of neurological dysfunction caused leading to depression and AD respectively
Fig. 6
Fig. 6
A possible pathogenesis of DE: Hyperglycaemia induced over production of iNOS has been reported leading to neuronal and insulin signalling impairment; however, implication of NMDAR is not clear
Fig. 7
Fig. 7
Microglia-neuron interaction: Hyperactivity of neurons induced by T2DM brings about an increase in the demand for energy to be utilised for the influx of glucose. Neurons then secrete latent microglial activators such as matrix metalloproteinase-9 (MMP-9), ATP and chemokines (for example CX3CL1). These activators then target the p38 MAPK signalling by enhancing it which leads to the increase in the inflammation. The destructive increase in inflammation causes elevated oxidative stress and cognitive dysfunction thus causing DE
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