Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging

Abstract

The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.

PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

“…Both 1TC and 2-tissue-compartment models were used to estimate pancreas and spleen V T . Spleen V T was used as an index of nondisplaceable uptake to calculate binding potential (BP ND , the ratio of specific to nonspecific radioligand concentration (15)), as has been proposed previously (16,17). Reference region methods were also investigated to quantify radioligand uptake without the need for arterial sampling.…”

Futility of attempts to detect and quantify beta cells by PET imaging in the pancreas: why it is time to abandon the approach

“…We would like to note that the study by Cline et al [19] is just one example of many in the literature that have used PET imaging to quantify beta cell mass [13][14][15][21][22][23][24][25][26] and we have expressed our views on these studies in the form of several letters to the editor [27,28]. We hope that by continuing to communicate our views on this subject (which are shared by others [20,29,30]) to the scientific community, we will soon abandon the unjustified use of PET imaging in the native pancreas in diabetes research and improve the validity of future research in this domain.…”

“…The authors reported a large spread of 18 F-FP-(+)-DTBZ binding and uptake variables in the pancreas of the HOV and participants with prediabetes overlapping with the type 2 diabetes participants. Unfortunately, the data described by Cline et al suffer from the deficiencies that we have described in the literature over the years [19]. The authors fail to discuss how the volume and the function of beta cells in the pancreas were measured.…”

“…As a recent example, the study reported by Cline et al in this issue of Diabetologia [19] describes the use of PET imaging with [ 18 F]fluoropropyl-(+)-dihydrotetrabenazine ( 18 F-FP-(+)-DTBZ) for assessing the correlation of beta cell mass (BCM) and its function in individuals with impaired glucose tolerance (prediabetes) or type 2 diabetes and age-BMI-matched healthy obese volunteers (HOV). In doing so, the authors aimed to test the hypothesis that a loss of BCM contributes to impaired insulin secretion in humans with type 2 diabetes.…”

“…The authors have discussed the issue of non-specific binding, which is a main source of error in the quantification of uptake of PET tracers by beta cells. They indicate that by using splenic uptake as a reference region, they have overcome the serious issue of non-specific binding in the pancreas [19]. However, we must point out that non-specific uptake of these compounds is primarily confined to the acinar tissue of the pancreas and the metabolic activity of these cells is completely different from that of the spleen, which is related to the bone marrow and lymphatic system.…”