title: Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans.
abstract: BACKGROUND
  Food addiction is a debated topic in neuroscience. Evidence suggests diabetes is related to reduced basal dopamine levels in the nucleus accumbens, similar to persons with drug addiction. It is unknown whether insulin sensitivity is related to endogenous dopamine levels in the ventral striatum of humans. We examined this using the agonist dopamine D2/3 receptor radiotracer [(11)C]-(+)-PHNO and an acute dopamine depletion challenge. In a separate sample of healthy persons, we examined whether dopamine depletion could alter insulin sensitivity.
  
  
  METHODS
  Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. Eleven healthy nonobese and nondiabetic persons (3 female) provided a baseline [(11)C]-(+)-PHNO scan, 9 of which provided a scan under dopamine depletion, allowing estimates of endogenous dopamine at dopamine D2/3 receptor. Dopamine depletion was achieved via alpha-methyl-para-tyrosine (64mg/kg, P.O.). In 25 healthy persons (9 female), fasting plasma and glucose was acquired before and after dopamine depletion.
  
  
  RESULTS
  Endogenous dopamine at ventral striatum dopamine D2/3 receptor was positively correlated with insulin sensitivity (r(7)=.84, P=.005) and negatively correlated with insulin levels (r(7)=-.85, P=.004). Glucose levels were not correlated with endogenous dopamine at ventral striatum dopamine D2/3 receptor (r(7)=-.49, P=.18). Consistently, acute dopamine depletion in healthy persons significantly decreased insulin sensitivity (t(24)=2.82, P=.01), increased insulin levels (t(24)=-2.62, P=.01), and did not change glucose levels (t(24)=-0.93, P=.36).
  
  
  CONCLUSIONS
  In healthy individuals, diminished insulin sensitivity is related to less endogenous dopamine at dopamine D2/3 receptor in the ventral striatum. Moreover, acute dopamine depletion reduces insulin sensitivity. These findings may have important implications for neuropsychiatric populations with metabolic abnormalities.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Borlido
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (Mr Caravaggio, Ms Borlido, Ms Feng, Dr Gerretsen, Dr Nakajima, Mr Plitman, Mr Chung, Dr Iwata, Dr Wilson, Dr Remington, and Dr Graff-Guerrero); Institute of Medical Science (Mr Caravaggio, Dr Hahn, Mr Fervaha, Dr Gerretsen, Mr Plitman, Mr Chung, Dr Wilson, Dr Remington, and Dr Graff-Guerrero), and Department of Psychiatry (Drs Hahn, Gerretsen, Nakajima, Iwata, Wilson, Remington, and Graff-Guerrero), University of Toronto, Toronto, Ontario, Canada. ariel.graff@camh.ca.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D002250:Carbon Radioisotopes / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000008:administration & dosage / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors; D066328:Ventral Striatum / Q000378:metabolism*; D055815:Young Adult; D019805:alpha-Methyltyrosine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007328:Insulin; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D019805:alpha-Methyltyrosine; D004298:Dopamine
keywords: D2; diabetes; dopamine; glucose; insulin