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Transthyretin and amyloid in the islets of Langerhans in type-2 diabetes.

Westermark GT, Westermark P - Exp Diabetes Res (2008)

Bottom Line: Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells.In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR.It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden. per.westermark@genpat.uu.se

ABSTRACT
Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.

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Related in: MedlinePlus

Normal human islets immunolabeled with antisera against: (a)transthyretin and (b) glucagon. In (c) is shown a normal humanislet, subjected to in situ hybridization with a TTR probe,visualized with immunohistochemistry. Note that positive cells havea distribution indicative of glucagon cells. Bar 20 μm. (d)shows a part of a glucagon cell with typical granules. The sectionwas double immunolabeled for glucagon (10 nm gold particles) and TTR(5 nm gold particles). Immunolabeling for both these substances isseen on the granules, bar 500 nm.
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fig2: Normal human islets immunolabeled with antisera against: (a)transthyretin and (b) glucagon. In (c) is shown a normal humanislet, subjected to in situ hybridization with a TTR probe,visualized with immunohistochemistry. Note that positive cells havea distribution indicative of glucagon cells. Bar 20 μm. (d)shows a part of a glucagon cell with typical granules. The sectionwas double immunolabeled for glucagon (10 nm gold particles) and TTR(5 nm gold particles). Immunolabeling for both these substances isseen on the granules, bar 500 nm.

Mentions: In sections of pancreata withoutamyloid from nondiabetic individuals, both antisera A1898 and A1899 labeledislet cells in a similar way. A strong reaction was seen in all islets withcells with a preferentially peripheral distribution (Figure 2(a)) When comparedwith sections immunostained for glucagon, an identical distribution was seen(Figure 2(b)). In addition, the majority of remaining islet cells, mainly betacells, were also labeled but only weakly (Figure 2(a)). In situ hybridizationexhibited clear expression of TTR in cells which had a distribution of alphacells only and no certain reactivity was found with beta cells (Figure 2(c)).Electron microscopicallyglucagon cells are characterized by secretory vesicles with a rounded electrondense core often situated somewhat eccentrically on the rest of the granule. Glucagonimmunoreactivity occurred in both these areas of the granules while TTR labelingwas mainly seen in the less electron dense parts of the alpha cell granules(Figure 2(d)). Small gold particles were also seen in the translucent areas of betacells but only to a small extent (not shown.). Antisera against insulin and IAPPlabeled normal beta cells as described [30].


Transthyretin and amyloid in the islets of Langerhans in type-2 diabetes.

Westermark GT, Westermark P - Exp Diabetes Res (2008)

Normal human islets immunolabeled with antisera against: (a)transthyretin and (b) glucagon. In (c) is shown a normal humanislet, subjected to in situ hybridization with a TTR probe,visualized with immunohistochemistry. Note that positive cells havea distribution indicative of glucagon cells. Bar 20 μm. (d)shows a part of a glucagon cell with typical granules. The sectionwas double immunolabeled for glucagon (10 nm gold particles) and TTR(5 nm gold particles). Immunolabeling for both these substances isseen on the granules, bar 500 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553203&req=5

fig2: Normal human islets immunolabeled with antisera against: (a)transthyretin and (b) glucagon. In (c) is shown a normal humanislet, subjected to in situ hybridization with a TTR probe,visualized with immunohistochemistry. Note that positive cells havea distribution indicative of glucagon cells. Bar 20 μm. (d)shows a part of a glucagon cell with typical granules. The sectionwas double immunolabeled for glucagon (10 nm gold particles) and TTR(5 nm gold particles). Immunolabeling for both these substances isseen on the granules, bar 500 nm.
Mentions: In sections of pancreata withoutamyloid from nondiabetic individuals, both antisera A1898 and A1899 labeledislet cells in a similar way. A strong reaction was seen in all islets withcells with a preferentially peripheral distribution (Figure 2(a)) When comparedwith sections immunostained for glucagon, an identical distribution was seen(Figure 2(b)). In addition, the majority of remaining islet cells, mainly betacells, were also labeled but only weakly (Figure 2(a)). In situ hybridizationexhibited clear expression of TTR in cells which had a distribution of alphacells only and no certain reactivity was found with beta cells (Figure 2(c)).Electron microscopicallyglucagon cells are characterized by secretory vesicles with a rounded electrondense core often situated somewhat eccentrically on the rest of the granule. Glucagonimmunoreactivity occurred in both these areas of the granules while TTR labelingwas mainly seen in the less electron dense parts of the alpha cell granules(Figure 2(d)). Small gold particles were also seen in the translucent areas of betacells but only to a small extent (not shown.). Antisera against insulin and IAPPlabeled normal beta cells as described [30].

Bottom Line: Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells.In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR.It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, Linköping University, 581 85 Linköping, Sweden. per.westermark@genpat.uu.se

ABSTRACT
Transthyretin (TTR) is a major amyloid fibril protein in certain systemic forms of amyloidosis. It is a plasma protein, mainly synthesized by the liver but expression occurs also at certain minor locations, including the endocrine cells in the islets of Langerhans. With the use of immunohistochemistry and in situ hybridization, we have studied the distribution of transthyretin-containing cells in islets of Langerhans in type-2 diabetic and nondiabetic individuals. TTR expression was particularly seen in alpha (glucagon) cells. Islets from type-2 diabetic patients had proportionally more transthyretin-reactive islet cells, including beta cells. A weak transthyretin immunoreaction in IAPP-derived amyloid occurred in some specimens. In seeding experiments in vitro, we found that TTR fibrils did not seed IAPP while IAPP fibrils seeded TTR. It is suggested that islet expression of transthyretin may be altered in type-2 diabetes.

Show MeSH
Related in: MedlinePlus