Impact of hyperinsulinemia on mammary gland development and inflammatory microenvironment

Active Project Grant Awarded Last action

Award ID
F31HD122353
Recipient
Awarding agency
Obligated
$82,158

Award facts

Completion date 0% complete
Originally
Place of performance
Minneapolis, MN 55455, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Insulin signaling is a crucial modulator of the mammary gland alveolar switch, the differentiation and maturation of alveoli into milk-secreting cells, during pregnancy. In obesity, there is improper mammary gland development, which is supported by clinical observations of mothers with obesity having poor lactation outcomes. Obesity is a complex disease that is accompanied by hyperinsulinemia and chronic inflammation; however, the complexity makes IT challenging to isolate its effects on mammary gland development and function. The long-term goal of this research is to understand the mechanisms of how maternal hyperinsulinemia and inflammation shape the dynamics of mammary gland alveolar switch and function. Our preliminary data indicate that hyperinsulinemia is associated with reduced insulin receptor Β (IRΒ) protein expression and P-AKT(S473) in mammary gland lysates, suggesting impaired insulin signaling. In addition, we have found that there is extensive alveolar growth at baseline, non-pregnant and pregnant phases of mammary gland development in hyperinsulinemia. The central hypothesis of this F31 is that hyperinsulinemia causes reduced insulin signaling and leads to dysregulated mammary gland alveolar switch due to insulin resistance and inflammation. The main objective of this proposal is to identify the mechanisms of dysregulated mammary gland alveolar switch by hyperinsulinemia and inflammation during pregnancy. Specific aim 1 will evaluate the impact of hyperinsulinemia on insulin signaling in the mammary gland during pregnancy. Specific aim 2 will investigate the role of hyperinsulinemia-induced inflammatory microenvironment in the regulation of the mammary gland alveolar switch. This F31 proposal is innovative because there are no clear molecular mechanisms on how hyperinsulinemia and inflammation affect the mammary gland alveolar switch during pregnancy. Successful completion of this proposal will reveal the mechanisms linking hyperinsulinemia and inflammation to mammary gland regulation and dysfunction, and identify therapeutic opportunities to improve lactation outcomes. This proposal incorporates new and timely training in conceptual knowledge on mammary gland physiology, inflammation, lactation, and technical skills such as flow cytometry, RNA SEQ bioinformatics, confocal microscopy, lactation lipidomic and proteomics assays to facilitate successful completion. Additional training includes scientific communication in oral and written formats, as well as teaching opportunities, to become a successful academic. All technical resources and key mentors have been identified at the university of minnesota to ensure the successful completion of the F31 award and achieve MR. Brian akhaphong's academic and career goals to secure a competitive postdoctoral position.

Transactions

Action Obligated Date
Amendment $41,079
Amendment $41,079
Original award $0

Quick answers

Who received award F31HD122353?

F31HD122353 was awarded to Regents Of The University Of Minnesota by National Institute of Child Health and Human Development (National Institutes of Health) on December 1, 2026.

How much is award F31HD122353 worth?

$82,158 has been obligated on F31HD122353.

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