Insulin resistance in acanthosis nigricans
Steven Feldman, MD, PhD
Saturday, 14 Oct 2023
11:15 – 11:35 CEST
Acanthosis nigricans is characterized by thickened velvety hyperpigmented plaques, most commonly the axilla, neck, and groin. Acanthosis nigricans has been associated with certain prescription medications and malignancy but is most commonly associated with obesity and insulin resistance. In this presentation, we will delve into the role of insulin resistance in acanthosis nigricans.
Insulin and its receptors are key players in acanthosis nigricans. Insulin-like growth factor 1 (IGF1) is structurally similar to insulin and can be synthesized in the skin. Ordinarily, insulin binds with high affinity to the insulin receptor, exerting metabolic effects, while IGF1 binds with the highest affinity to the IGF1 receptor, promoting mitogenic effects. However, in individuals with metabolic imbalances, elevated insulin levels can disrupt the balance and directly stimulate the IGF1 receptor on keratinocytes and dermal fibroblasts, resulting in acanthosis, hyperkeratosis, and papillomatosis.
Leptin, encoded by the Obese (Ob) gene, is a protein hormone primarily secreted by adipose cells and may also play a role in acanthosis nigricans. Leptin can interact with Insulin receptor substrates, promoting insulin sensitivity and reducing insulin levels.
However, in cases of obesity, elevated leptin levels can act as a pro-inflammatory cytokine and lead to insulin resistance. This resistance, in turn, drives increased insulin levels, further promoting leptin synthesis and release. This creates a feedforward mechanism involving obesity, leptin, and insulin, resulting in a state of hyperinsulinemia and hyperleptinemia. Leptin receptors in acanthosis nigricans lesions-affected tissue are upregulated. Proliferation induced by leptin, along with the proliferation stimulated by the IGF receptor, may contribute to the development of acanthosis nigricans.
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