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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 (a) is shown an islet from a type-2 diabetic individual. Thereis pronounced IAPP amyloid infiltration, weakly labeled withantibodies against TTR. (b) shows a small islet in a nondiabeticindividual with familial TTR-amyloidosis. There are heavy depositsof TTR-amyloid outside the islet but no islet amyloid. A  =  amyloid.Immunolabeled with antiserum against TTR.
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fig5: In (a) is shown an islet from a type-2 diabetic individual. Thereis pronounced IAPP amyloid infiltration, weakly labeled withantibodies against TTR. (b) shows a small islet in a nondiabeticindividual with familial TTR-amyloidosis. There are heavy depositsof TTR-amyloid outside the islet but no islet amyloid. A = amyloid.Immunolabeled with antiserum against TTR.

Mentions: Islet amyloid from diabetic andnondiabetic individuals exhibited a strong immunolabeling with antiserumagainst IAPP (not shown). Since we have shown previously that commerciallyavailable antibodies against TTR often do not recognize TTR in fibrillar (i.e.,amyloid) form, we developed two different rabbit antisera which both stronglylabeled cellular TTR and TTR in amyloid. The two TTR antisera labeled isletamyloid weakly in some cases (Figures 3(d) and 5(a)). This staining was evenand no areas with strong reaction were seen. In the electron microscopic study,IAPP antiserum labeled amyloid in the diabetic case, but no certain binding ofTTR antibodies to fibrils was seen. In order to study the specificity of thereaction in amyloid, we used an amyloid array with tissues from severalpatients in one block. The two TTR antisera showed reaction only with amyloidof known TTR origin (i.e., Swedish familial amyloidosis and SSA) but not withamyloid of AA, AL, AMed, or Aβ nature, showing thatTTR-immunoreactivity is not a general feature of amyloid deposits.


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

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

In (a) is shown an islet from a type-2 diabetic individual. Thereis pronounced IAPP amyloid infiltration, weakly labeled withantibodies against TTR. (b) shows a small islet in a nondiabeticindividual with familial TTR-amyloidosis. There are heavy depositsof TTR-amyloid outside the islet but no islet amyloid. A  =  amyloid.Immunolabeled with antiserum against TTR.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: In (a) is shown an islet from a type-2 diabetic individual. Thereis pronounced IAPP amyloid infiltration, weakly labeled withantibodies against TTR. (b) shows a small islet in a nondiabeticindividual with familial TTR-amyloidosis. There are heavy depositsof TTR-amyloid outside the islet but no islet amyloid. A = amyloid.Immunolabeled with antiserum against TTR.
Mentions: Islet amyloid from diabetic andnondiabetic individuals exhibited a strong immunolabeling with antiserumagainst IAPP (not shown). Since we have shown previously that commerciallyavailable antibodies against TTR often do not recognize TTR in fibrillar (i.e.,amyloid) form, we developed two different rabbit antisera which both stronglylabeled cellular TTR and TTR in amyloid. The two TTR antisera labeled isletamyloid weakly in some cases (Figures 3(d) and 5(a)). This staining was evenand no areas with strong reaction were seen. In the electron microscopic study,IAPP antiserum labeled amyloid in the diabetic case, but no certain binding ofTTR antibodies to fibrils was seen. In order to study the specificity of thereaction in amyloid, we used an amyloid array with tissues from severalpatients in one block. The two TTR antisera showed reaction only with amyloidof known TTR origin (i.e., Swedish familial amyloidosis and SSA) but not withamyloid of AA, AL, AMed, or Aβ nature, showing thatTTR-immunoreactivity is not a general feature of amyloid deposits.

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