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   https://doi.org/10.1038/s41467-022-35176-7  

   Dall’Agnese, Alessandra; Platt, Jesse M.; Zheng, Ming M.; Friesen, Max; Dall’Agnese, Giuseppe; Blaise, Alyssa M.; Spinelli, Jessica B.; Henninger, Jonathan E.; Tevonian, Erin N.; Hannett, Nancy M.; et al (December 2022, Nature Communications)

   Abstract Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches. 

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2. Engineering glucose-responsive insulin

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   Zeng, Yi; Wang, Jinqiang; Gu, Zhongze; Gu, Zhen (September 2019, Medicine in Drug Discovery)

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3. Advances in transdermal insulin delivery

   https://doi.org/10.1016/j.addr.2018.12.006  

   Zhang, Yuqi; Yu, Jicheng; Kahkoska, Anna R.; Wang, Jinqiang; Buse, John B.; Gu, Zhen (January 2019, Advanced Drug Delivery Reviews)
4. Glucose‐Responsive Insulin and Delivery Systems: Innovation and Translation

   https://doi.org/10.1002/adma.201902004  

   Wang, Jinqiang; Wang, Zejun; Yu, Jicheng; Kahkoska, Anna_R; Buse, John_B; Gu, Zhen (August 2019, Advanced Materials)

   Abstract Type 1 and advanced type 2 diabetes treatment involves daily injections or continuous infusion of exogenous insulin aimed at regulating blood glucose levels in the normoglycemic range. However, current options for insulin therapy are limited by the risk of hypoglycemia and are associated with suboptimal glycemic control outcomes. Therefore, a range of glucose‐responsive components that can undergo changes in conformation or show alterations in intermolecular binding capability in response to glucose stimulation has been studied for ultimate integration into closed‐loop insulin delivery or “smart insulin” systems. Here, an overview of the evolution and recent progress in the development of molecular approaches for glucose‐responsive insulin delivery systems, a rapidly growing subfield of precision medicine, is presented. Three central glucose‐responsive moieties, including glucose oxidase, phenylboronic acid, and glucose‐binding molecules are examined in detail. Future opportunities and challenges regarding translation are also discussed. 

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5. The causal effect of obesity on prediabetes and insulin resistance reveals the important role of adipose tissue in insulin resistance

   https://doi.org/10.1371/journal.pgen.1009018  

   Miao, Zong; Alvarez, Marcus; Ko, Arthur; Bhagat, Yash; Rahmani, Elior; Jew, Brandon; Heinonen, Sini; Muñoz-Hernandez, Linda Liliana; Herrera-Hernandez, Miguel; Aguilar-Salinas, Carlos; et al (September 2020, PLOS Genetics)

   Hauser, Elizabeth R. (Ed.)