title: Enhanced cholinergic response in pancreata of nonhuman primates with impaired glucose tolerance shown on [18F]fluorobenzyltrozamicol positron emission tomography.
abstract: BACKGROUND
  Islet cell adaptation to insulin resistance in type 2 diabetes mellitus may be due in part to increased stimulation of beta cells by the autonomic nervous system. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor correlates with cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. In this study, we utilize [18F]FBT PET to demonstrate pancreatic cholinergic activity before and after dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT) glucose tolerance.
  
  
  METHODS
  Seven adult female vervet (Chlorocebus aethiops) monkeys were maintained on an atherogenic Western diet. They were divided into two groups: four with NGT and three with IGT. Each subject underwent [18F]FBT PET twice: first, a baseline PET under fasting conditions; and second, PET under fasting conditions but after intravenous infusion of dextrose solution. Quantitative analysis of pancreatic uptake at 60 min post-injection was performed.
  
  
  RESULTS
  There was no difference in pancreatic uptake of [18F]FBT on baseline scans between the two groups. Pancreatic uptake of [18F]FBT increased in every subject after dextrose infusion (P = 0.03). On post-dextrose PET scans, pancreatic uptake of [18F]FBT was significantly higher in IGT subjects compared with NGT subjects (P = 0.03). The post-dextrose to pre-dextrose uptake ratios were higher in IGT subjects (P = 0.08).
  
  
  CONCLUSIONS
  Acute increases in pancreatic cholinergic activity in vivo were detected in the pancreata of nonhuman primates with NGT and IGT after intravenous dextrose infusion on [18F]FBT PET. In subjects with IGT, this activity was significantly higher, suggesting increased autonomic nervous system stimulation of the pancreatic islets in insulin-resistant subjects.
authors: Department of Radiology/Nuclear Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA. pbclark@wfubmc.edu
authors: Paige B
authors: PB
authors: Clark
authors: Kylie
authors: K
authors: Kavanagh
authors: H Donald
authors: HD
authors: Gage
authors: Pradeep
authors: P
authors: Garg
authors: Sudha
authors: S
authors: Garg
authors: Jorge
authors: J
authors: Calles-Escandon
authors: Janice D
authors: JD
authors: Wagner
authors: Kathryn
authors: K
authors: Morton
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D018149:Glucose Intolerance / Q000097:blood / Q000000981:diagnostic imaging*; D007328:Insulin / Q000097:blood; D010880:Piperidines; D049268:Positron-Emission Tomography / Q000379:methods*; D011323:Primates; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D007328:Insulin; D010880:Piperidines; D014280:Triglycerides; C087277:4-fluorobenzyltrozamicol