title: (18)F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults.
abstract: OBJECTIVE
  Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue (18)F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography.
  
  
  METHODS
  In nine healthy adults (18)F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 °C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp.
  
  
  RESULTS
  Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p=0.7). Similarly there were no differences in mean standardized (18)F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 °C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones.
  
  
  CONCLUSIONS
  This study shows that there is a similar amount of (18)F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: j.e.schopman@gmail.com.
authors.forename: Josefine E
authors.initials: JE
authors.lastname: Schopman
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Admiraal
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Soeters
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology and Radiochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter L H T
authors.initials: PL
authors.lastname: Bisschop
authors.affiliation: Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Frier
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joost B L
authors.initials: JB
authors.lastname: Hoekstra
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Holleman
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D003080:Cold Temperature; D003920:Diabetes Mellitus / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D061385:Insulins / Q000378:metabolism*; D008297:Male; D022722:Thermogenesis / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D061385:Insulins; D019788:Fluorodeoxyglucose F18
keywords: Brown adipose tissue; Hypoglycemia; Hypothermia; Non-shivering thermogenesis