Insulin receptor plays a central role in skin carcinogenesis by regulating cytoskeleton assembly.

Diabetes mellitus prevalence is increasing rapidly and is a major cause of mortality and morbidity worldwide. In addition to the known severe complications associated with the disease, in recent years diabetes has been recognized as a major risk factor for cancer. Patients with diabetes experience significantly higher incidence of and higher mortality rates from many types of cancer.

Insulin analogues display atypical differentiative activities in skin keratinocytes.

Background: We have previously shown that both insulin and IGF1 lead to increased proliferation of keratinocytes. However, whereas insulin supports keratinocytes differentiation, IGF1 inhibits this process. The aim of the present study was to examine the proliferative and differentiative effects of insulin analogues (glargine, detemir, lispro and aspart) in primary keratinocytes in comparison with insulin and IGF1.

Two novel mutations identified in familial cases with Donohue syndrome.

Donohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We report the clinical, molecular, and biochemical characterization of three new patients with DS, and address genotype-phenotype issues playing a role in the pathophysiology of DS. A female infant born to first-degree cousins Muslim Arab parents and two brothers born to first-degree cousins Druze parents presented classical features of DS with hypertrophic cardiomyopathy and died in infancy.

Insulin receptor substrate 1 (IRS-1) plays a unique role in normal epidermal physiology.

Insulin receptor substrate (IRS) proteins play a central role in insulin signaling. Previously we have demonstrated that insulin is essential for normal skin development and function. In the present study we investigated the involvement of the IRS-1 and IRS-2 proteins in skin physiology and in mediating insulin action in skin.

Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation.

The insulin-like growth factor 1 receptor (IGF-1R) is a multifunctional receptor that mediates signals for cell proliferation, differentiation, and survival. Genetic experiments showed that IGF-1R inactivation in skin results in a disrupted epidermis. However, because IGF-1R-null mice die at birth, it is difficult to study the effects of IGF-1R on skin.

Insulin receptor substrate 2 plays diverse cell-specific roles in the regulation of glucose transport.

The insulin receptor substrate 2 (IRS-2) protein is one of the major insulin-signaling substrates. In the present study, we investigated the role of IRS-2 in skin epidermal keratinocytes and dermal fibroblasts. Although skin is not a classical insulin target tissue, we have previously demonstrated that insulin, via the insulin receptor, is essential for normal skin cell physiology.