REVIEW: Canonical and Non-Canonical Mechanisms of Insulin-Dependent Signaling Regulating Adipogenic Differentiation in Adipose Tissue Renewal

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Andrey D. Bondarev¹, Konstantin Yu. Kulebyakin¹, Nikolai B. Gusev², and Pyotr A. Tyurin-Kuzmin^1,a*

¹Department of Biochemistry and Regenerative Biomedicine, Faculty of Medicine, Medical Research and Educational Institute, Lomonosov Moscow State University, 119991 Moscow, Russia

²Department of Biochemistry, School of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 23, 2025; Revised: September 24, 2025; Accepted: October 4, 2025

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Insulin exerts a complex effect on metabolism, cell growth, and differentiation interacting with its receptor. Adipose tissue is one of the key targets for insulin; in this tissue insulin regulates the processes of energy storage, as well as tissue renewal and emergence of new adipocytes. Insulin activates conversion of glucose into fatty acids, inhibits lipolysis, and induces adipogenic differentiation of adipose tissue stem cells. The insulin receptor is a classic tyrosine kinase receptor that activate phosphoinositide-3-kinase and mitogen-activated protein kinase signaling cascades. At the same time, insulin receptor activates several non-canonical signaling cascades that determine features of the receptor functioning. For example, insulin can affect phosphoinositide metabolism, as well as calcium and redox-dependent signaling. In addition, the insulin receptor can also interact with the trimeric G proteins-coupled receptors (GPCRs). Here, we review canonical and non-canonical signaling cascades activated by the insulin receptor and molecular mechanisms of their involvement in regulating the human adipose tissue renewal.

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KEY WORDS: insulin, intracellular signaling, calcium signaling, redox signaling, multipotent mesenchymal stromal cells

DOI: 10.1134/S0006297925603727

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