Enhanced cholinergic response in pancreata of nonhuman primates with impaired glucose tolerance shown on [18F]fluorobenzyltrozamicol positron emission tomography.
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.
Clark
Paige B
PB
Department of Radiology/Nuclear Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA. pbclark@wfubmc.edu
Kavanagh
Kylie
K
Gage
H Donald
HD
Garg
Pradeep
P
Garg
Sudha
S
Calles-Escandon
Jorge
J
Wagner
Janice D
JD
Morton
Kathryn
K
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
D001786:Blood Glucose; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D007328:Insulin; D010880:Piperidines; D014280:Triglycerides; C087277:4-fluorobenzyltrozamicol