Lipid Metabolism and Membrane Composition Are Altered in the Brains of Type II Diabetic Mice

Tapas K. Makar, Basaligappa L. Hungund, George Cook, Khosrow Kashfi, Arthur J.L. Cooper

Research output: Contribution to journalArticle

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Abstract

Abstract: CBL/57 strain db/db mice exhibit type II (non‐insulin‐dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane‐bound synaptosomal acetylcholinesterase, Na+,K+‐ATPase, and Mg2+‐ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes—monoamine oxidase B and citrate synthase—and a cytosolic enzyme—lactate dehydrogenase—are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1‐14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.

Original languageEnglish (US)
Pages (from-to)2159-2168
Number of pages10
JournalJournal of Neurochemistry
Volume64
Issue number5
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Lipid Metabolism
Brain
Membranes
Chemical analysis
Mitochondria
Mitochondrial Membranes
Medical problems
Fatty Acids
Carnitine O-Acetyltransferase
Pyruvate Dehydrogenase Complex
Carnitine O-Palmitoyltransferase
Ca(2+) Mg(2+)-ATPase
Oxidation
Nerve Endings
Carnitine
Palmitates
Acetylcholinesterase
Glutamine
Metabolism
Aspartic Acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Lipid Metabolism and Membrane Composition Are Altered in the Brains of Type II Diabetic Mice. / Makar, Tapas K.; Hungund, Basaligappa L.; Cook, George; Kashfi, Khosrow; Cooper, Arthur J.L.

In: Journal of Neurochemistry, Vol. 64, No. 5, 01.01.1995, p. 2159-2168.

Research output: Contribution to journalArticle

Makar, Tapas K. ; Hungund, Basaligappa L. ; Cook, George ; Kashfi, Khosrow ; Cooper, Arthur J.L. / Lipid Metabolism and Membrane Composition Are Altered in the Brains of Type II Diabetic Mice. In: Journal of Neurochemistry. 1995 ; Vol. 64, No. 5. pp. 2159-2168.
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N2 - Abstract: CBL/57 strain db/db mice exhibit type II (non‐insulin‐dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane‐bound synaptosomal acetylcholinesterase, Na+,K+‐ATPase, and Mg2+‐ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes—monoamine oxidase B and citrate synthase—and a cytosolic enzyme—lactate dehydrogenase—are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1‐14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.

AB - Abstract: CBL/57 strain db/db mice exhibit type II (non‐insulin‐dependent) diabetes. The affected mice are markedly hyperinsulinemic, hyperglycemic, and hypercholesterolemic, and their serum K+ levels are decreased. The brains of the diabetic mice are significantly smaller than those of their lean, control littermates, but the protein concentration is normal. The low brain weight is accompanied by a loss of major fatty acid components within the whole brain, nerve endings, and mitochondrial membranes. Cholesterol levels are low in whole brain but are not significantly different from normal in the synaptosomal membranes. The phospholipid concentration is significantly decreased in whole brain homogenates, crude synaptosomal membranes, and crude mitochondrial membranes of the diabetic mice. In addition, the specific activities of membrane‐bound synaptosomal acetylcholinesterase, Na+,K+‐ATPase, and Mg2+‐ATPase are decreased in crude synaptosomal membranes of the diabetic mice. The specific activities of carnitine palmitoyltransferase I and carnitine acetyltransferase are significantly increased in the crude mitochondrial fraction isolated from the brains of the type II diabetic mice, whereas the specific activity of pyruvate dehydrogenase complex is decreased. The specific activities of two other mitochondrial enzymes—monoamine oxidase B and citrate synthase—and a cytosolic enzyme—lactate dehydrogenase—are unaltered. The ability to synthesize cyclic AMP is markedly decreased in the brains of the diabetic mice. The concentrations of carnitine and of the amino acids, glutamate, aspartate, glutamine, and serine are unaltered, whereas glycine levels are significantly elevated in the brains of the db/db mice. The data suggest that in vivo the brains of the diabetic mice exhibit a decreased capacity for glucose oxidation and increased capacity for fatty acid oxidation. This hypothesis is supported by the finding that cerebral mitochondria isolated from the db/db mice oxidize [1‐14C]palmitate to 14CO2 at a rate almost twice that of control mitochondria. The present findings emphasize the potentially serious alteration of brain metabolism in uncontrolled type II diabetes.

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