Increased brain monocarboxylic acid transport and utilization in type 1 diabetes.
We hypothesized that increased capacity for brain utilization of nonglucose substrates (monocarboxylic acids [MCAs]) by upregulation of the MCA transporters may contribute metabolic substrates during hypoglycemia. To test this hypothesis, we assessed brain acetate metabolism in five well-controlled type 1 diabetic subjects and six nondiabetic control subjects using 13C magnetic resonance spectroscopy during infusions of [2-(13)C]acetate during hypoglycemia (approximately 55 mg/dl). Acetate is transported into the brain through MCA transporters that are also used for lactate and ketones. Brain acetate concentrations were over twofold higher in the subjects with diabetes than the control subjects (P = 0.01). The fraction of oxidative metabolism from acetate (P = 0.015) and the rate of MCA transport (P = 0.01) were also approximately twofold higher in the diabetic subjects. We conclude that during hypoglycemia MCA transport in the brain was increased by approximately twofold in patients with well-controlled type 1 diabetes, as reflected by higher brain acetate concentrations and rates of acetate oxidation. This upregulation would potentially allow a similar twofold increase in the transport of other MCAs, including lactate, during insulin-induced hypoglycemia. These data are consistent with the hypothesis that upregulation of MCA transport may contribute to the maintenance of brain energetics during hypoglycemia in patients with type 1 diabetes.
Department of Psychiatry and Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06536-8012, USA.
Graeme F
GF
Mason
Kitt F
KF
Petersen
Vincent
V
Lebon
Douglas L
DL
Rothman
Gerald I
GI
Shulman
D000085:Acetates / Q000378:metabolism*; D000328:Adult; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D007328:Insulin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid