Mendelian randomization analysis demonstrates the causal effects of IGF family members in diabetes

IGFBP7 has been found to play an important role in inflammatory diseases, such as acute lung injury (ALI). However, the role of IGFBP7 in different stages of inflammation remains unclear. Transcriptome sequencing was used to identify the regulatory genes of IGFBP7, and endothelial IGFBP7 expression was knocked down using Aplnr-Dre mice to evaluate the endothelial proliferation capacity. The expression of proliferation-related genes was detected by western blotting and RT-PCR assays. In this study, we found that knockdown of IGFBP7 in endothelial cells significantly decreases the expression of endothelial cell proliferation-related genes and cell number in the recovery phase but not in the acute phase of ALI. Mechanistically, using bulk-RNA sequencing and CO-IP, we found that IGFBP7 promotes phosphorylation of FOS and subsequently upregulates YAP1 molecules, thereby promoting endothelial cell proliferation. This study indicated that IGFBP7 has diverse roles in different stages of ALI, which extends the understanding of IGFBP7 in different stages of ALI and suggests that IGFBP7 as a potential therapeutic target in ALI needs to take into account the period specificity of ALI.

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Glucose metabolism outcomes after pituitary surgery in patients with acromegaly

Pascual-Corrales,

Biagetti,

Marazuela

et al. 2024

Preprint

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Aim: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. Methods: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. Results: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had type 2 diabetes mellitus (T2DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9). In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), artropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-1 levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of T2DM. At the last follow-up visit after surgery, 21.1% of the T2DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of T2DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). Conclusion: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

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Mendelian randomization analysis demonstrates the causal effects of IGF family members in diabetes

Cited by 3 publications

References 30 publications

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly

IGFBP7 promotes endothelial cell repair in the recovery phase of acute lung injury

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly

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