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PMID: 16710474 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model.

The Journal of clinical investigation ·Vol. 116 ·No. 6 ·2006-06-00 ·Pages 1506-13

Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE

Abstract

Diabetes results from an absolute or relative reduction in pancreatic beta cell mass (BCM) leading to insufficient insulin secretion and hyperglycemia. Measurement of insulin secretory capacity is currently used as a surrogate measure of BCM. However, serum insulin concentrations provide an imprecise index of BCM, and no reliable noninvasive measure of BCM is currently available. Type 2 vesicular monoamine transporters (VMAT2) are expressed in human islet beta cells, as well as in tissues of the CNS. [11C]Dihydrotetrabenazine ([11C]DTBZ) binds specifically to VMAT2 and is a radioligand currently used in clinical imaging of the brain. Here we report the use of [11C]DTBZ to estimate BCM in a rodent model of spontaneous type 1 diabetes (the BB-DP rat). In longitudinal PET studies of the BB-DP rat, we found a significant decline in pancreatic uptake of [11C]DTBZ that anticipated the loss of glycemic control. Based on comparison of standardized uptake values (SUVs) of [11C]DTBZ and blood glucose concentrations, loss of more than 65% of the original SUV correlated significantly with the development of persistent hyperglycemia. These studies suggest that PET-based quantitation of VMAT2 receptors provides a noninvasive measurement of BCM that could be used to study the pathogenesis of diabetes and to monitor therapeutic interventions.

MeSH Terms
Animals Blood Glucose/metabolism Carbon Radioisotopes/metabolism Diabetes Mellitus, Type 1/pathology Disease Models, Animal Humans Insulin/blood Insulin-Secreting Cells/cytology,metabolism Male Papio Positron-Emission Tomography/methods Radioligand Assay Rats Rats, Inbred BB Rats, Sprague-Dawley Tetrabenazine/analogs & derivatives,chemistry,metabolism Tissue Distribution Vesicular Monoamine Transport Proteins/metabolism
Chemicals
Blood Glucose Carbon Radioisotopes Insulin Slc18a2 protein, rat Vesicular Monoamine Transport Proteins dihydrotetrabenazine Tetrabenazine
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Souza Fabiola
Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA.
Simpson Norman
Raffo Anthony
Saxena Chitra
Maffei Antonella
Hardy Mark
Kilbourn Michael
Goland Robin
Leibel Rudolph
Mann J John
Van Heertum Ronald
Harris Paul E
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI27645
Published
2006-06-00
Epub
2006-00-18
Pages
1506-13
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1462946
Subset
IM
Grants
NINDS NIH HHS · P01 NS015655 · United States
NIDDK NIH HHS · 5 P30 DK063608-04 · United States
NIDDK NIH HHS · R01 DK063567 · United States
NINDS NIH HHS · 2 R01 NS15655 · United States
NIDDK NIH HHS · 2 R01 DK63567-03 · United States
NIDDK NIH HHS · P30 DK063608 · United States
Telethon · GJT04003 · Italy
External Links
PubMed source DOI: 10.1172/JCI27645 PMC Full Text View journal details
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