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Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas.

Saisho Y, Harris PE, Butler AE, Galasso R, Gurlo T, Rizza RA, Butler PC - J. Mol. Histol. (2008)

Bottom Line: Most beta cells expressed VMAT2.In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining.However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells.

View Article: PubMed Central - PubMed

Affiliation: Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 900 Weyburn Place #A, Los Angeles, CA, 90024-2852, USA.

ABSTRACT
Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for insulin, VMAT2 and other pancreatic hormones. Most beta cells expressed VMAT2. VMAT2 expression was not changed by the presence of diabetes. In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining. However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells. Although VMAT2 was not excluded as a target for beta cell mass measurement, expression of VMAT2 in PP cells predicts residual VMAT2 expression in human pancreas even in the absence of beta cells.

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(a) Bundle of VMAT2 positive nerve fibers surrounded by connective tissue in the pancreas. VMAT2, red; DAPI (nucleus), blue. (b) VMAT2 positive nerve fibers (arrowhead), but not VMAT2 positive cells (asterisks) were co-stained with neuron marker (green). Neuron marker (NeuN and Tuj-1), green; VMAT2, red; DAPI (nucleus), blue. Original magnification: 20×. Scale bars = 30 μm. Images are from a recent onset T1DM case
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Fig6: (a) Bundle of VMAT2 positive nerve fibers surrounded by connective tissue in the pancreas. VMAT2, red; DAPI (nucleus), blue. (b) VMAT2 positive nerve fibers (arrowhead), but not VMAT2 positive cells (asterisks) were co-stained with neuron marker (green). Neuron marker (NeuN and Tuj-1), green; VMAT2, red; DAPI (nucleus), blue. Original magnification: 20×. Scale bars = 30 μm. Images are from a recent onset T1DM case

Mentions: However, 39 ± 7% of islet PP positive cells also expressed VMAT2 (Figs. 4g–i, 5). Co-localization of PP and VMAT2 was confirmed by confocal microscopy (Fig. 5a–c). VMAT2 positive PP cells were more frequent in scattered groups of PP cells in the exocrine pancreas compared to the PP cells within islets. As expected PP cells were most abundant in the head of the pancreas where VMAT2 positive PP cells were therefore also most frequent (~70% of PP cells) (Fig. 4g–i). Triple staining for PP, insulin and VMAT2 revealed that most of the VMAT2 positive-insulin negative cells could be accounted for as PP cells (Fig. 5d–g). Only ~1% of VMAT2 positive cells were negative for both insulin and PP (Fig. 5g), and were most likely mast cells or possibly nerve cells (Fig. 6). We detected no co-localization of PP and insulin (Fig. 5).Fig. 5


Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas.

Saisho Y, Harris PE, Butler AE, Galasso R, Gurlo T, Rizza RA, Butler PC - J. Mol. Histol. (2008)

(a) Bundle of VMAT2 positive nerve fibers surrounded by connective tissue in the pancreas. VMAT2, red; DAPI (nucleus), blue. (b) VMAT2 positive nerve fibers (arrowhead), but not VMAT2 positive cells (asterisks) were co-stained with neuron marker (green). Neuron marker (NeuN and Tuj-1), green; VMAT2, red; DAPI (nucleus), blue. Original magnification: 20×. Scale bars = 30 μm. Images are from a recent onset T1DM case
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Related In: Results  -  Collection

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Fig6: (a) Bundle of VMAT2 positive nerve fibers surrounded by connective tissue in the pancreas. VMAT2, red; DAPI (nucleus), blue. (b) VMAT2 positive nerve fibers (arrowhead), but not VMAT2 positive cells (asterisks) were co-stained with neuron marker (green). Neuron marker (NeuN and Tuj-1), green; VMAT2, red; DAPI (nucleus), blue. Original magnification: 20×. Scale bars = 30 μm. Images are from a recent onset T1DM case
Mentions: However, 39 ± 7% of islet PP positive cells also expressed VMAT2 (Figs. 4g–i, 5). Co-localization of PP and VMAT2 was confirmed by confocal microscopy (Fig. 5a–c). VMAT2 positive PP cells were more frequent in scattered groups of PP cells in the exocrine pancreas compared to the PP cells within islets. As expected PP cells were most abundant in the head of the pancreas where VMAT2 positive PP cells were therefore also most frequent (~70% of PP cells) (Fig. 4g–i). Triple staining for PP, insulin and VMAT2 revealed that most of the VMAT2 positive-insulin negative cells could be accounted for as PP cells (Fig. 5d–g). Only ~1% of VMAT2 positive cells were negative for both insulin and PP (Fig. 5g), and were most likely mast cells or possibly nerve cells (Fig. 6). We detected no co-localization of PP and insulin (Fig. 5).Fig. 5

Bottom Line: Most beta cells expressed VMAT2.In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining.However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells.

View Article: PubMed Central - PubMed

Affiliation: Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 900 Weyburn Place #A, Los Angeles, CA, 90024-2852, USA.

ABSTRACT
Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for insulin, VMAT2 and other pancreatic hormones. Most beta cells expressed VMAT2. VMAT2 expression was not changed by the presence of diabetes. In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining. However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells. Although VMAT2 was not excluded as a target for beta cell mass measurement, expression of VMAT2 in PP cells predicts residual VMAT2 expression in human pancreas even in the absence of beta cells.

Show MeSH
Related in: MedlinePlus