HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mason, G. F. Articles by Shulman, G. I. Search for Related Content PubMed PubMed Citation Articles by Mason, G. F. Articles by Shulman, G. I. Social Bookmarking                What's this?

Increased Brain Monocarboxylic Acid Transport and Utilization in Type 1 Diabetes

¹ Department of Psychiatry and Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut
² Department of Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut
³ Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
⁴ Groupe de Spectroscopie RMN, Unité d’Imagerie Isotopique Biochimique et Pharmacologique, Orsay Cedex, France
⁵ Department of Biomedical Engineering, Yale School of Medicine, New Haven, Connecticut
⁶ Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale School of Medicine, New Haven, Connecticut

Address correspondence and reprint requests to Dr. Gerald I. Shulman, Howard Hughes Medical Institute, Yale University School of Medicine, TAC S-269, P.O. Box 9812, New Haven, CT 06536-8012. E-mail: gerald.shulman{at}yale.edu

Abbreviations: MCA, monocarboxylic acid; MRS, magnetic resonance spectroscopy; PET, positron emission tomography; TCA, tricarboxylic acid

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 [2-¹³C]acetate during hypoglycemia (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 appoximately 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. S. Sherwin Bringing Light to the Dark Side of Insulin: A Journey Across the Blood-Brain Barrier Diabetes, September 1, 2008; 57(9): 2259 - 2268. [Full Text] [PDF]