Obesity and Type 2 Diabetes in Rats Are Associated with Altered Brain Glycogen and Amino-acid Homeostasis

Overview

Journal J Cereb Blood Flow Metab

Publisher Sage Publications

Specialties Cardiology & Vascular Diseases
Endocrinology
Neurology

Date 2010 Apr 29

PMID 20424632

Citations 48

Authors

Helle M Sickmann

Helle S Waagepetersen

Arne Schousboe

Andrew J Benie

Stephan D Bouman

Affiliations

Soon will be listed here.

Abstract

Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected by these conditions. [1-(13)C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague-Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with (13)C-labeling and content of glutamate, glutamine, GABA, aspartate, and alanine. Blood glucose concentrations and (13)C enrichment were determined. (13)C-labeling in glutamate was lower in ZO and ZDF rats in comparison with the controls. The molecular carbon labeling (MCL) ratio between alanine and glutamate was higher in the ZDF rats. The MCL ratios of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA cycle was more decreased than glycolytic activity. Furthermore, reduced glutamate-glutamine cycling was also observed in the obese and type 2 diabetic states.

Citing Articles

Oral Supplements of Combined Lactobacillus plantarum and Asparagus officinalis Modulate Gut Microbiota and Alleviate High-Fat Diet-Induced Cognitive Deficits and Neurodegeneration in Rats.

Shahin N, Ahmed-Farid O, Sakr E, Kamel E, Mohamed M Probiotics Antimicrob Proteins. 2025; .

PMID: 39777720 DOI: 10.1007/s12602-024-10429-7.

Oxidative Stress Markers and Na,K-ATPase Enzyme Kinetics Are Altered in the Cerebellum of Zucker Diabetic Fatty fa/fa Rats: A Comparison with Lean fa/+ and Wistar Rats.

Radosinska D, Gaal Kovalcikova A, Gardlik R, Chomova M, Snurikova D, Radosinska J Biology (Basel). 2024; 13(10).

PMID: 39452068 PMC: 11505095. DOI: 10.3390/biology13100759.

Augmented Mitochondrial Transfer Involved in Astrocytic PSPH Attenuates Cognitive Dysfunction in db/db Mice.

Ma H, He S, Li Y, Zhang X, Chang H, Du M Mol Neurobiol. 2024; 61(11):8872-8885.

PMID: 38573412 DOI: 10.1007/s12035-024-04064-0.

Evaluating the Diagnostic Value of Electrovestibulography (EVestG) in Alzheimer's Patients with Mixed Pathology: A Pilot Study.

Dastgheib Z, Lithgow B, Moussavi Z Medicina (Kaunas). 2023; 59(12).

PMID: 38138194 PMC: 10744488. DOI: 10.3390/medicina59122091.

Diet-induced diabetes is associated with lower hippocampal glycogen and reduced glycogenolysis following local exogenous insulin.

McNay E J Neurochem. 2023; 168(5):760-764.

PMID: 37885343 PMC: 11045660. DOI: 10.1111/jnc.16001.

References

Oz G, Kumar A, Rao J, Kodl C, Chow L, Eberly L . Human brain glycogen metabolism during and after hypoglycemia. Diabetes. 2009; 58(9):1978-85. PMC: 2731528. DOI: 10.2337/db09-0226. View

Kamal A, Biessels G, Gispen W, Ramakers G . Synaptic transmission changes in the pyramidal cells of the hippocampus in streptozotocin-induced diabetes mellitus in rats. Brain Res. 2006; 1073-1074:276-80. DOI: 10.1016/j.brainres.2005.12.070. View

Gjedde A, Crone C . Blood-brain glucose transfer: repression in chronic hyperglycemia. Science. 1981; 214(4519):456-7. DOI: 10.1126/science.7027439. View

MARFAING-JALLAT P, Levacher C, Calando Y, Picon L, Penicaud L . Glucose utilization and insulin binding in discrete brain areas of obese rats. Physiol Behav. 1992; 52(4):713-6. DOI: 10.1016/0031-9384(92)90402-n. View

Garcia-Espinosa M, Garcia-Martin M, Cerdan S . Role of glial metabolism in diabetic encephalopathy as detected by high resolution 13C NMR. NMR Biomed. 2003; 16(6-7):440-9. DOI: 10.1002/nbm.843. View

Zielke H, Zielke C, Baab P, Tildon J . Effect of fluorocitrate on cerebral oxidation of lactate and glucose in freely moving rats. J Neurochem. 2007; 101(1):9-16. DOI: 10.1111/j.1471-4159.2006.04335.x. View

Seaquist E, Tkac I, Damberg G, Thomas W, Gruetter R . Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Metabolism. 2005; 54(8):1008-13. DOI: 10.1016/j.metabol.2005.02.018. View

Bak L, Schousboe A, Sonnewald U, Waagepetersen H . Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab. 2006; 26(10):1285-97. DOI: 10.1038/sj.jcbfm.9600281. View

Bhardwaj S, Sharma P, Kaur G . Alterations in free radical scavenger system profile of type I diabetic rat brain. Mol Chem Neuropathol. 1999; 35(1-3):187-202. DOI: 10.1007/BF02815124. View

10.

Schousboe A, Sarup A, Bak L, Waagepetersen H, Larsson O . Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission. Neurochem Int. 2004; 45(4):521-7. DOI: 10.1016/j.neuint.2003.11.001. View

11.

Tsujii S, Nakai Y, Takahashi H, Usui T, Koh T, Yonekura Y . Effect of food deprivation on regional brain glucose utilization in lean and fatty Zucker rats. Brain Res. 1988; 475(2):371-5. DOI: 10.1016/0006-8993(88)90628-2. View

12.

Danbolt N . Glutamate uptake. Prog Neurobiol. 2001; 65(1):1-105. DOI: 10.1016/s0301-0082(00)00067-8. View

13.

Martinez-Tellez R, Gomez-Villalobos M, Flores G . Alteration in dendritic morphology of cortical neurons in rats with diabetes mellitus induced by streptozotocin. Brain Res. 2005; 1048(1-2):108-15. DOI: 10.1016/j.brainres.2005.04.048. View

14.

Pold R, Jensen L, Jessen N, Buhl E, Schmitz O, Flyvbjerg A . Long-term AICAR administration and exercise prevents diabetes in ZDF rats. Diabetes. 2005; 54(4):928-34. DOI: 10.2337/diabetes.54.4.928. View

15.

Sickmann H, Walls A, Schousboe A, Bouman S, Waagepetersen H . Functional significance of brain glycogen in sustaining glutamatergic neurotransmission. J Neurochem. 2009; 109 Suppl 1:80-6. DOI: 10.1111/j.1471-4159.2009.05915.x. View

16.

Gibbs M, Lloyd H, Santa T, Hertz L . Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. J Neurosci Res. 2007; 85(15):3326-33. DOI: 10.1002/jnr.21307. View

17.

Cruz N, Dienel G . High glycogen levels in brains of rats with minimal environmental stimuli: implications for metabolic contributions of working astrocytes. J Cereb Blood Flow Metab. 2002; 22(12):1476-89. DOI: 10.1097/01.WCB.0000034362.37277.C0. View

18.

Ottersen O . Quantitative electron microscopic immunocytochemistry of neuroactive amino acids. Anat Embryol (Berl). 1989; 180(1):1-15. DOI: 10.1007/BF00321895. View

19.

McCall A, Millington W, Wurtman R . Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus. Proc Natl Acad Sci U S A. 1982; 79(17):5406-10. PMC: 346906. DOI: 10.1073/pnas.79.17.5406. View

20.

Biessels G, Gispen W . The impact of diabetes on cognition: what can be learned from rodent models?. Neurobiol Aging. 2005; 26 Suppl 1:36-41. DOI: 10.1016/j.neurobiolaging.2005.08.015. View