PURPOSE OF REVIEW: The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases. RECENT FINDINGS: Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.

• Klíčová slova
• Bone marrow adipose tissue, Bone marrow mesenchymal stem cells, Insulin signaling, Marrow adiposity,
• MeSH
• adipogeneze MeSH
• buněčná diferenciace MeSH
• buňky kostní dřeně metabolismus   MeSH
• glukagonu podobný peptid 1 metabolismus   MeSH
• glukosa metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• metabolické nemoci kostí metabolismus   MeSH
• mezenchymální kmenové buňky metabolismus   MeSH
• obezita metabolismus   MeSH
• parathormon metabolismus   MeSH
• protein 4 vázající insulinu podobné růstové faktory metabolismus   MeSH
• proteiny insulinového receptorového substrátu metabolismus   MeSH
• receptor inzulinu metabolismus   MeSH
• receptor pro konečné produkty pokročilé glykace metabolismus   MeSH
• stárnutí buněk * MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• insulinu podobný růstový faktor I MeSH
• inzulin MeSH
• parathormon MeSH
• protein 4 vázající insulinu podobné růstové faktory MeSH
• proteiny insulinového receptorového substrátu MeSH
• receptor inzulinu MeSH
• receptor pro konečné produkty pokročilé glykace MeSH

A significant drawback of the exogenous administration of insulin to diabetics is the non-physiological profile of insulin action resulting in the insufficient suppression of hepatic glucose production, which is the main contributing factor to diabetic hyperglycemia under fasting conditions and the basis of the challenge to restore a more physiological glucose profile in diabetes. The insulin receptor (IR) exists in two alternatively spliced variants, IR-A and IR-B, with different tissue distribution. While peripheral tissues contain different proportions of both isoforms, hepatic cells almost exclusively contain IR-B. In this respect, IR-B-selective insulin analogs would be of great interest for their potential to restore more natural metabolic homeostasis in diabetes. Recent advances in the structural biology of insulin and IR have provided new clues for understanding the interaction of both proteins. This article discusses and offers some structural perspectives for the design of specific insulin analogs with a preferential binding to IR-B.

• Klíčová slova
• CT-peptide, IR-A, IR-B, binding affinity, exon 11, insulin analog, insulin receptor isoform,
• Publikační typ
• časopisecké články MeSH