The regulation of skin proliferation and differentiation in the IR null mouse: implications for skin complications of diabetes.

Abstract:

:Impaired wound healing of skin is one of the most serious complications of diabetes. However, the pathogenesis of this process is not known, and it is unclear whether impaired insulin signaling could directly affect skin physiology. To elucidate the role of insulin in skin, we studied skin insulin receptor (IR) null mice. The morphology of the skin of newborn IR null mice was normal; however, these mice exhibited decreased proliferation of skin keratinocytes and changes in expression of skin differentiation markers. Due to the short life span of the IR null mice, further characterization was performed in cultured skin keratinocytes that can be induced to differentiate in vitro, closely following the maturation pattern of epidermis in vivo. It was found that despite a compensatory increase in the insulin-like growth factor I receptor autophosphorylation, differentiation of cultured IR null keratinocytes was markedly impaired. In vitro proliferation was not affected as much. Furthermore, although the basal glucose transport system of the null mice was not defective, the insulin-induced increase in glucose transport was abrogated. These results suggest that insulin regulates, via the IR, the differentiation and glucose transport of skin keratinocytes, whereas proliferation is affected by the diabetes milieu of IR knockout mice.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Wertheimer E,Spravchikov N,Trebicz M,Gartsbein M,Accili D,Avinoah I,Nofeh-Moses S,Sizyakov G,Tennenbaum T

doi

10.1210/endo.142.3.7988

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

1234-41

issue

3

eissn

0013-7227

issn

1945-7170

journal_volume

142

pub_type

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