Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans

Fernando Caravaggio, Carol Borlido, Margaret Hahn, Zhe Feng, Gagan Fervaha, Philip Gerretsen, Shinichiro Nakajima, Eric Plitman, Jun Ku Chung, Yusuke Iwata, Alan Wilson, Gary Remington, Ariel Graff-Guerrero

Research output: Contribution to journalArticle

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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 [11C]-(+)-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 [11C]-(+)-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 (64 mg/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). Conclusion: 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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number7
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Fingerprint

Insulin Resistance
Dopamine
Dopamine D2 Receptors
Glucose
Insulin
Ventral Striatum
Fasting
alpha-Methyltyrosine
Nucleus Accumbens
Neurosciences
Substance-Related Disorders
Homeostasis
Food

Keywords

  • D2
  • Diabetes
  • Dopamine
  • Glucose
  • Insulin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans. / Caravaggio, Fernando; Borlido, Carol; Hahn, Margaret; Feng, Zhe; Fervaha, Gagan; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Chung, Jun Ku; Iwata, Yusuke; Wilson, Alan; Remington, Gary; Graff-Guerrero, Ariel.

In: International Journal of Neuropsychopharmacology, Vol. 18, No. 7, 01.01.2015, p. 1-10.

Research output: Contribution to journalArticle

Caravaggio, F, Borlido, C, Hahn, M, Feng, Z, Fervaha, G, Gerretsen, P, Nakajima, S, Plitman, E, Chung, JK, Iwata, Y, Wilson, A, Remington, G & Graff-Guerrero, A 2015, 'Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans', International Journal of Neuropsychopharmacology, vol. 18, no. 7, pp. 1-10. https://doi.org/10.1093/ijnp/pyv014
Caravaggio, Fernando ; Borlido, Carol ; Hahn, Margaret ; Feng, Zhe ; Fervaha, Gagan ; Gerretsen, Philip ; Nakajima, Shinichiro ; Plitman, Eric ; Chung, Jun Ku ; Iwata, Yusuke ; Wilson, Alan ; Remington, Gary ; Graff-Guerrero, Ariel. / Reduced insulin sensitivity is related to less endogenous dopamine at D2/3 receptors in the ventral striatum of healthy nonobese humans. In: International Journal of Neuropsychopharmacology. 2015 ; Vol. 18, No. 7. pp. 1-10.
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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 [11C]-(+)-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 [11C]-(+)-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 (64 mg/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). Conclusion: 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.",
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AU - Feng, Zhe

AU - Fervaha, Gagan

AU - Gerretsen, Philip

AU - Nakajima, Shinichiro

AU - Plitman, Eric

AU - Chung, Jun Ku

AU - Iwata, Yusuke

AU - Wilson, Alan

AU - Remington, Gary

AU - Graff-Guerrero, Ariel

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N2 - 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 [11C]-(+)-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 [11C]-(+)-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 (64 mg/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). Conclusion: 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.

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