Genetic Defects in Human Pericentrin Are Associated With Severe Insulin Resistance and Diabetes

The document summarizes a study that examined the connection between PCNT mutations, which cause Majewski osteodysplastic primordial dwarfism type II (MOPDII), and severe insulin resistance and diabetes. The cross-sectional metabolic assessment involved 21 patients with PCNT mutations, with 18 showing insulin resistance and 10 having early-onset diabetes. The study found that severe insulin resistance and diabetes are common in individuals with PCNT deficiency, but these conditions are not present at birth and develop during childhood or adolescence. In vitro experiments with 3T3-L1 preadipocytes indicated that pericentrin deficiency impairs adipocyte differentiation and insulin-stimulated glucose uptake, suggesting a role in metabolic homeostasis. The study concludes that PCNT defects lead to significant metabolic issues, including insulin resistance and dyslipidemia, which can result in early-onset diabetes. The study involved various sample sizes, with n=9 for adipocyte gene expression and n=3 or n=4 for cell proliferation rates.