Logroño. Spain, Feb 7 (EFE).— Researchers have identified the molecular mechanism by which the peptide hormone, adrenomedullin, triggers type 2 diabetes in obese persons, paving the way for new treatment and prevention strategies, according to a study published in Science.
Led by Germany’s Max Planck Institute, the study involved researchers from Germany, the United States, and Spain, including the Angiogenesis Unit at the Biomedical Research Center of La Rioja (Cibir). Alfredo Martínez, director of Cibir’s unit, presented the findings on Friday.
While previous research linked obesity to type 2 diabetes, the molecular mechanism behind this connection remained unknown.
Scientists have now demonstrated that fat cells in obese individuals produce excessive levels of adrenomedullin. This regulatory peptide interferes with insulin receptors in endothelial cells, those lining blood vessels, reducing their sensitivity to insulin and contributing to insulin resistance, Martínez said.
Insulin resistance, the hallmark of type 2 diabetes, restricts blood flow to glucose-absorbing organs such as the liver and muscles, further impairing blood sugar regulation.
Diabetes is a major global driver of illness, death, and healthcare costs, with the majority of cases linked to obesity-related insulin resistance and type 2 diabetes. This resistance primarily impacts key metabolic tissues, including skeletal muscle, fat, and the liver.
Blood vessel endothelial cells also contain insulin receptors, and their insulin signaling is believed to play a vital role in metabolic regulation. Research suggests that endothelial insulin resistance may contribute to overall insulin resistance in type 2 diabetes.
However, the exact mechanisms behind this process remain unclear, and its direct role in the disease has not been conclusively determined.
Genetic engineering confirms findings
Using advanced genetic engineering techniques, researchers developed conditional knockout models—mice in which the adrenomedullin gene or its receptor was deactivated in specific cells.
Results showed that obese mice with intact adrenomedullin pathways developed insulin resistance and type 2 diabetes, along with reduced blood flow to key organs.
However, those lacking the hormone in fat cells or its receptor in endothelial cells did not develop diabetes, despite being equally obese.
Moreover, researchers found that an adrenomedullin inhibitor prevented insulin resistance in obese mice, reinforcing the hormone’s role as a potential therapeutic target.
Scientists now see blocking adrenomedullin or its receptor as a promising new strategy for preventing type 2 diabetes, particularly in obese persons. EFE
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