Neuronal damage and cognitive impairment associated with hypoglycemia: An integrated view

Languren, Gabriela; Montiel, Teresa; Julio-Amilpas, Alberto; Massieu, Lourdes

doi:10.1016/j.neuint.2013.06.018

Cited by 110 publications

(85 citation statements)

References 128 publications

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“…The potential mechanisms for this include direct effects of hypo- or hyperglycaemia and hypo- or hyperinsulinemia and also indirect effects via cerebrovascular alterations [20, 21]. This study analyzed the role of saffron on the biochemical and behavioral function of diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

Samarghandian

Azimi‐Nezhad

Samini

2014

BioMed Research International

121

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Diabetic encephalopathy is one of the severe complications in patients with diabetes mellitus. Findings indicate that saffron extract has antioxidant properties but its underlying beneficial effects on diabetic encephalopathy were unclear. In the present study, the protective activities of saffron were evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly increased body weight and serum TNF-α and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation endproducts (AGEs) levels. Furthermore, significant increase in HDL and decrease (P < 0.05) in cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At the end of experiments, the hippocampus tissue was used for determination of glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but remarkably decreased cognitive deficit, serum TNF-α, and induced nitric oxide synthase (iNOS) activity in hippocampus tissue. Our findings indicated that saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce the oxidative stress in diabetic encephalopathy rats. This study suggested that saffron extract might be a promising candidate for the improvement of chemically induced diabetes and its complications.

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Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

Samarghandian

Azimi‐Nezhad

Samini

2014

BioMed Research International

121

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“…For example, because glucose is used efficiently in the brain in all the human tissues (Phelps 2000), the inhibitory effects caused by anesthetics and phenothiazines would preferentially appear on glucose transporters highly expressed in the brain. Glucose starvation in the brain, compulsively caused by these drugs, might account for the loss of consciousness during anesthesia, similar to hypoglycemic comas observed in diabetic patients (Languren et al 2013). In tissues with insufficient glucose transporters, phenotypes other than glucose starvation would appear.…”

Section: Inhibitory Effects Of Clinical Drugs On Glucose Transport Inmentioning

confidence: 88%

Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

et al. 2016

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Action mechanisms of anesthetics remain unclear because of difficulty in explaining how structurally different anesthetics cause similar effects. In Saccharomyces cerevisiae, local anesthetics and antipsychotic phenothiazines induced responses similar to those caused by glucose starvation, and they eventually inhibited cell growth. These drugs inhibited glucose uptake, but additional glucose conferred resistance to their effects; hence, the primary action of the drugs is to cause glucose starvation. In hxt 0 strains with all hexose transporter (HXT) genes deleted, a strain harboring a single copy of HXT1 (HXT1s) was more sensitive to tetracaine than a strain harboring multiple copies (HXT1m), which indicates that quantitative reduction of HXT1 increases tetracaine sensitivity. However, additional glucose rather than the overexpression of HXT1/2 conferred tetracaine resistance to wild-type yeast; therefore, Hxts that actively transport hexoses apparently confer tetracaine resistance. Additional glucose alleviated sensitivity to local anesthetics and phenothiazines in the HXT1m strain but not the HXT1s strain; thus, the glucose-induced effects required a certain amount of Hxt1. At low concentrations, fluorescent phenothiazines were distributed in various membranes. At higher concentrations, they destroyed the membranes and thereby delocalized Hxt1-GFP from the plasma membrane, similar to local anesthetics. These results suggest that the aforementioned drugs affect various membrane targets via nonspecific interactions with membranes. However, the drugs preferentially inhibit the function of abundant Hxts, resulting in glucose starvation. When Hxts are scarce, this preference is lost, thereby mitigating the alleviation by additional glucose. These results provide a mechanism that explains how different compounds induce similar effects based on lipid theory.

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“…Recent neuroimaging studies support this view [25••, 47]. Severe hypoglycemia is a likely mechanism [25••], as it is associated with neuronal damage in the hippocampus [48] and with learning and memory [49••, 50]. A recent study by Hershey et al [51] found abnormal enlargement of the hippocampus in children with T1D associated with severe hypoglycemic episodes.…”

Section: Effects Of Diabetes During Different Developmental Periodsmentioning

confidence: 99%

Neurocognitive Outcomes in Pediatric Diabetes: a Developmental Perspective

et al. 2014

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The impact of diabetes on the developing brain is well-accepted. Effects on neurocognitive functioning are moderate but have larger functional implications, especially when considered through a developmental lens. Pathophysiological factors such as severe hypoglycemia and chronic hyperglycemia can alter developmental trajectories in early childhood and perhaps at later periods. In this paper, we selectively review neurocognitive outcomes in pediatric diabetes (largely type 1), integrating recent research from developmental neuroscience and neuroimaging. We examine the effects of diabetes at different stages and place findings within a neurodevelopmental diathesis/stress framework. Early-onset diabetes is associated with specific effects on memory and more global cognitive late-effects, but less is known about cognitive outcomes of diabetes in later childhood and in adolescence, a time of increased neurobehavioral vulnerability that has received relatively limited empirical attention. Studies are also needed to better elucidate risk and protective factors that may moderate neurodevelopmental outcomes in youth with diabetes.

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Neuronal damage and cognitive impairment associated with hypoglycemia: An integrated view

Cited by 110 publications

References 128 publications

Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

Ameliorative Effect of Saffron Aqueous Extract on Hyperglycemia, Hyperlipidemia, and Oxidative Stress on Diabetic Encephalopathy in Streptozotocin Induced Experimental Diabetes Mellitus

Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

Neurocognitive Outcomes in Pediatric Diabetes: a Developmental Perspective

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