期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 116, 期 6, 页码 1506-1513出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI27645
关键词
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资金
- NIDDK NIH HHS [2 R01 DK63567-03, R01 DK063567, P30 DK063608, 5 P30 DK063608-04] Funding Source: Medline
- NINDS NIH HHS [P01 NS015655, 2 R01 NS15655] Funding Source: Medline
- Telethon [GJT04003] Funding Source: Medline
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. [C-11]Dihydrotetrabenazine ([C-11]DTBZ) binds specifically to VMAT2 and is a radioligand currently used in clinical imaging of the brain. Here we report the use of [C-11]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 [C-11]DTBZ that anticipated the loss of glycemic control. Based on comparison of standardized uptake values (SUVs) of [C-11]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.
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