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High Blood Glucose and Damage to Neuronal Tissue

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Handbook of Behavior, Food and Nutrition

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Abstract

Type-1, type-2, and gestational/embryonic diabetes are all damaging and impair the nervous system. All three forms of diabetes cause oxidative stress, apoptosis, and neuropathy. In type-1 and type-2 diabetes (T2D), oxidative stress and apoptosis involve excessive release of glutamate, activation of N-methyl-d-aspartate (NMDA) receptors, increased cytoplasmic Ca+2 levels, and complex signaling pathways leading to apoptosis. Neuropathy has also been associated with a reduction in a number of neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), and the use of exogenous BDNF and GDNF in ameliorating type-1 and type-2 diabetic symptoms has been reported. While several regions of the brain are affected, the hypothalamus and hippocampus are key areas of neuropathy. While less understood, gestational diabetes also causes oxidative stress and apoptosis within fetal brains and embryonic hyperglycemia is associated with hyperhomocysteinemia and subsequent apoptosis. Elevated embryonic homocysteine (HoCys) levels promote membrane lipid peroxidation, apoptosis, and are teratogenic in chicks. Data presented in this review indicate that embryonic hyperglycemia inhibits both the remethylation pathway, which is largely dependent on 5-methyltetrahydrofolate levels, and the transsulfuration pathway, which removes HoCys ultimately to α-ketobutyrate, glutathione, and taurine. HoCys is of interest because HoCys is both an agonist and antagonist of NMDA receptors.

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Abbreviations

AChE:

Acetylcholine esterase

BDNF:

Brain-derived neurotrophic factor

ChAT:

Choline acetyltransferase

DHA:

Docosahexaenoic acid

10-FTHF DH:

10-formyltetrahydrofolate dehydrogenase

10-FTHF hydrolase:

10-formyltetrahydrofolate hydrolase

GDNF:

Glial cell line-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

GLUTS:

Glucose transporters

HoCys:

Homocysteine

5-Methyl THF:

5-methyltetrahydrofolate

NTDs:

Neural tube defects

NMDA:

N-methyl-d-aspartate

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

STZ:

Streptozocin

TBARS:

Thiobarbituric acid reactive substances

T1D:

Type-1 diabetes

T2D:

Type-2 diabetes

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Acknowledgments

I am very thankful for the superb technical assistance of Ms. Kelly Colesman and Ms. Sarah Yearsley who performed the taurine, 10-FTHF DH, and 10-FTHF hydrolase assays (Tables 173.1 and 173.2; Figs. 173.3, 173.4, 173.5, and 173.6). This article is dedicated to the memories of Grace, Evelyn, and Robert Miller, Sr.

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  1. Biology Department, Hillsdale College, 278 N. West St., Dow Science 213, Hillsdale, MI, 49242-1205, USA

    Robert R. Miller Jr.

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Editors and Affiliations

  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

  2. Arizona Health Science Center, Mel and Enid Zuckerman College of Public, University of Arizona, 1501 N. Campbell Ave. Room 4335, Tucson, 85724-5155, Arizona, USA

    Ronald Ross Watson

  3. University of the West of Scotland, Ayr Campus, Ayr, KA8 0SR, United Kingdom

    Colin R. Martin

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Miller, R.R. (2011). High Blood Glucose and Damage to Neuronal Tissue. In: Preedy, V., Watson, R., Martin, C. (eds) Handbook of Behavior, Food and Nutrition. Springer, New York, NY. https://doi.org/10.1007/978-0-387-92271-3_173

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