Small-molecule inhibition of inflammatory β-cell death

Morten Lundh; S S Scully; T Mandrup-Poulsen; B K Wagner

doi:10.1111/dom.12158

Small-molecule inhibition of inflammatory β-cell death

Morten Lundh, S S Scully, T Mandrup-Poulsen, B K Wagner

Endocrinology and Metabolism

9 Citationer (Scopus)

Abstract

With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.

Originalsprog	Engelsk
Tidsskrift	Diabetes, Obesity and Metabolism Online
Vol/bind	15
Udgave nummer	3
Sider (fra-til)	176-84
Antal sider	9
ISSN	1463-1326
DOI	https://doi.org/10.1111/dom.12158
Status	Udgivet - sep. 2013

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10.1111/dom.12158

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abstract = "With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.",

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AU - Scully, S S

AU - Mandrup-Poulsen, T

AU - Wagner, B K

PY - 2013/9

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N2 - With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.

AB - With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes.

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DO - 10.1111/dom.12158

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JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 3

ER -

Small-molecule inhibition of inflammatory β-cell death

Abstract

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