American Diabetes Association Research Symposium: Diabetes and the Brain

Abstract

From 28–30 October 2011, more than 100 people assembled in Alexandria, Virginia, to participate in an American Diabetes Association–sponsored research symposium entitled “Diabetes and the Brain.” The objective of the symposium was to discuss the role of the brain in normal and abnormal metabolism and to consider the impact of diabetes on cerebral structure and function. Symposium participants were particularly interested in understanding how abnormalities in brain metabolism could affect the development of diabetes and obesity and how these diseases could, in turn, affect learning and memory. The growing epidemic of diabetes brought urgency to the meeting because of the ever-increasing number of people placed at risk for the cerebral complications of the disease. In this report, we present meeting highlights in five related areas as follows: 1) metabolism, blood flow, and epigenetics; 2 ) glucose sensing and hypoglycemia counterregulation; 3) insulin resistance and action in the brain; 4) neurocognition and imaging; and 5 ) energy homeostasis. The symposium opened with an outstanding review of cerebral metabolism by Gerald Dienel, PhD, from the University of Arkansas. He emphasized that glucose is the major fuel for the adult brain and that it has multifunctional roles in brain function. Metabolism of glucose via the glycolytic, pentose phosphate shunt, and tricarboxylic acid cycle pathways provides ATP for energy, NADPH for defense against oxidative stress, and carbon for biosynthesis of amino acids and sugars used for synthesis of glycoproteins and glycolipids and for de novo synthesis of tricarboxylic acid cycle-derived neurotransmitters glutamate and γ-aminobutyric acid (GABA) (Fig. 1). Glycogen is stored predominately in astrocytes, and the CO2 fixation reaction required for glutamate biosynthesis occurs in astrocytes. Local rates of blood flow and glucose utilization are closely linked to local activities of brain cells, and metabolic rates increase with increased functional activity and decline when cellular …