title: Brain glucose sensing and neural regulation of insulin and glucagon secretion.
abstract: Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at ∼ 5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainly in the brainstem and the hypothalamus. Activation of these neurons by hyper- or hypoglycemia represents a critical aspect of the control of glucose homeostasis, and loss of glucose sensing by these cells as well as by pancreatic β-cells is a hallmark of type 2 diabetes. In this article, aspects of the brain-endocrine pancreas axis are reviewed, highlighting the importance of central glucose sensing in the control of counterregulation to hypoglycemia but also mentioning the role of the neural control in β-cell mass and function. Overall, the conclusions of these studies is that impaired glucose homeostasis, such as associated with type 2 diabetes, but also defective counterregulation to hypoglycemia, may be caused by initial defects in glucose sensing.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland. Bernard.thorens@unil.ch
authors.forename: B
authors.initials: B
authors.lastname: Thorens
mesh_terms: D001341:Autonomic Nervous System / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005934:Glucagon / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D005934:Glucagon