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Cerebral glutamate metabolism during hypoglycaemia in healthy and type 1 diabetic humans
Author(s) -
Bischof M. G.,
Brehm A.,
Bernroider E.,
Krššák M.,
Mlynárik V.,
Krebs M.,
Roden M.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01615.x
Subject(s) - medicine , endocrinology , creatine , glutamine , choline , type 1 diabetes , glutamate receptor , glucose uptake , diabetes mellitus , chemistry , insulin , biochemistry , receptor , amino acid
Background The mechanisms responsible for the progressive failure of hypoglycaemia counterregulation in long‐standing type 1 diabetes are poorly understood. Increased brain glucose uptake during hypoglycaemia or alterations of brain energy metabolism could effect glucose sensing by the brain and thus contribute to hypoglycaemia‐associated autonomic failure. Materials and methods Type 1 diabetic patients (T1DM) and healthy volunteers (CON) were studied before, during and after a hypoglycaemic (50 mg dL −1 ) hyperinsulinaemic (1·5 mU kg −1 min −1 ) clamp test. The 1 H magnetic resonance spectroscopy of the occipital lobe of the brain was performed employing the STEAM localization technique. The water signal was suppressed by the modified SWAMP method. All spectra were acquired on a 3 Tesla scanner (80 cm MEDSPEC‐DBX, Bruker Medical, Ettlingen, Germany) using a 10‐cm diameter surface coil. Results During hypoglycaemia, T1DM showed blunted endocrine counterregulation. At baseline the brain tissue glucose : creatine ratio was lower in CON than in T1DM (CON 0·13 ± 0·05 vs. T1DM 0·19 0·11; P < 0·01). During hypoglycaemia glucose : creatine ratios decreased in both groups (CON 0·07 ± 0·08, P < 0·05; T1DM 0·03 ± 0·03, P < 0·001). A significant drop in the glutamate : creatine ratio could only be found in CON during hypoglycaemia (CON 1·36 ± 0·08 vs. 1·26 ± 0·11; P < 0·01; T1DM 1·32 ± 0·13 vs. 1·28 ± 0·15; P = NS). The ratios of glutamine, N‐acetylaspartate, choline and myo‐inositol : creatine were not different between both groups and did not change throughout the experiment. Conclusions Only in CON does moderate hypoglycaemia reduce intracerebral glutamate concentrations, possibly owing to a slower substrate flux through the tricarboxylic acid cycle in neurones. The maintenance of normal energy metabolism in T1DM during hypoglycaemia might effect glucose sensing in the brain and contribute to hypoglycaemia‐associated autonomic failure.