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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

In vitro seeding and cross-seeding experiments with TTR and IAPPmeasured with thioflavin T. Preformed fibrils of IAPP seeded TTR(blue circles) and IAPP (red triangles, insert). No other increasein signals occurred. Thus, TTR fibrils did not seed IAPP (redcircles).
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fig6: In vitro seeding and cross-seeding experiments with TTR and IAPPmeasured with thioflavin T. Preformed fibrils of IAPP seeded TTR(blue circles) and IAPP (red triangles, insert). No other increasein signals occurred. Thus, TTR fibrils did not seed IAPP (redcircles).

Mentions: Fibril formation of many amyloidproteins, including TTR and IAPP, occursspontaneously in vitro after a lag phase which varies in length depending onprotein. Seeding with preformed fibrils can shorten the lag phase considerably,which was seen most evidently when a solution of IAPP was seeded with IAPP fibrils(Figure 6, inserted). TTR fibrils did not induce any increase in fluorescencesignal when incubated with newly dissolved TTR or solubilized IAPP (Figure 6).However, IAPP fibrils had a clear effect on TTR after a lag phase of about 3hours (Figure 6).


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

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

In vitro seeding and cross-seeding experiments with TTR and IAPPmeasured with thioflavin T. Preformed fibrils of IAPP seeded TTR(blue circles) and IAPP (red triangles, insert). No other increasein signals occurred. Thus, TTR fibrils did not seed IAPP (redcircles).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: In vitro seeding and cross-seeding experiments with TTR and IAPPmeasured with thioflavin T. Preformed fibrils of IAPP seeded TTR(blue circles) and IAPP (red triangles, insert). No other increasein signals occurred. Thus, TTR fibrils did not seed IAPP (redcircles).
Mentions: Fibril formation of many amyloidproteins, including TTR and IAPP, occursspontaneously in vitro after a lag phase which varies in length depending onprotein. Seeding with preformed fibrils can shorten the lag phase considerably,which was seen most evidently when a solution of IAPP was seeded with IAPP fibrils(Figure 6, inserted). TTR fibrils did not induce any increase in fluorescencesignal when incubated with newly dissolved TTR or solubilized IAPP (Figure 6).However, IAPP fibrils had a clear effect on TTR after a lag phase of about 3hours (Figure 6).

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