Effects of a selective serotonin reuptake inhibitor, fluoxetine, on counterregulatory responses to hypoglycemia in healthy individuals.
OBJECTIVE
Hypoglycemia commonly occurs in intensively-treated diabetic patients. Repeated hypoglycemia blunts counterregulatory responses, thereby increasing the risk for further hypoglycemic events. Currently, physiologic approaches to augment counterregulatory responses to hypoglycemia have not been established. Therefore, the specific aim of this study was to test the hypothesis that 6 weeks' administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine would amplify autonomic nervous system (ANS) and neuroendocrine counterregulatory mechanisms during hypoglycemia.


METHODS
A total of 20 healthy (10 male and 10 female) subjects participated in an initial single-step hyperinsulinemic (9 pmol . kg(-1) . min(-1))-hypoglycemic (means +/- SE 2.9 +/- 0.1 mmol/l) clamp study and were then randomized to receive 6 weeks' administration of fluoxetine (n = 14) or identical placebo (n = 6) in a double-blind fashion. After 6 weeks, subjects returned for a second hypoglycemic clamp. Glucose kinetics were determined by three-tritiated glucose, and muscle sympathetic nerve activity (MSNA) was measured by microneurography.


RESULTS
Despite identical hypoglycemia (2.9 +/- 0.1 mmol/l) and insulinemia during all clamp studies, key ANS (epinephrine, norepinephrine, and MSNA but not symptoms), neuroendocrine (cortisol), and metabolic (endogenous glucose production, glycogenolysis, and lipolysis) responses were increased (P < 0.01) following fluoxetine.


CONCLUSIONS
This study demonstrated that 6 weeks' administration of the SSRI fluoxetine can amplify a wide spectrum of ANS and metabolic counterregulatory responses during hypoglycemia in healthy individuals. These data further suggest that serotonergic transmission may be an important mechanism in modulating sympathetic nervous system drive during hypoglycemia in healthy individuals.
Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
Vanessa J
VJ
Briscoe
Andrew C
AC
Ertl
Donna B
DB
Tate
Sheila
S
Dawling
Stephen N
SN
Davis
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D000409:Alanine / Q000097:blood; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000097:blood; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000097:blood
D020155:3-Hydroxybutyric Acid; D000409:Alanine; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005473:Fluoxetine; D005990:Glycerol; D007328:Insulin; D019344:Lactic Acid; D017367:Selective Serotonin Reuptake Inhibitors