Akt's acute regulation of hepatic glucose utilization Megan Stefkovich

Format:

Book

Thesis/Dissertation

Author/Creator:

Stefkovich, Megan, author.

Contributor:

University of Pennsylvania. Cell and Molecular Biology., degree granting institution.

Language:

English

Subjects (All):

Cellular biology.

Physiology.

Biochemistry.

Endocrinology.

0379.

0487.

0409.

0719.

Local Subjects:

Cellular biology.

Physiology.

Biochemistry.

Endocrinology.

0379.

0487.

0409.

0719.

Genre:

Academic theses

Physical Description:

1 online resource (105 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

The liver is a crucial organ for maintaining blood glucose homeostasis. It plays an essential role by producing and exporting glucose during fasting and taking up glucose for storage and metabolism postprandially. Glucose production and catabolism are catalyzed by almost all the same metabolic reactions, but run in opposite directions, and so must be carefully coordinated to avoid futile glucose cycling. Hormonal control of this balancing act has long been observed. Postprandial release of insulin drives catabolism by stimulating the liver's postprandial response and suppressing its fasting response, within minutes. The current explanation as to how it achieves this is through transcriptional control of glycolytic and gluconeogenic enzyme expression via the serine/threonine kinase AKT. The comparatively slow process of transcription, however, does not explain the rapid time scale by which insulin inhibits glucose release and stimulates uptake in the liver, suggesting alternative mechanisms. My thesis aims to determine the effect that acute insulin and AKT signaling has on glucose metabolism in the liver. I explored the hypothesis that AKT acutely promotes glucose utilization in hepatocytes, independent of transcriptional control. To test this, I used a combination of stable isotope tracing and pharmacological inhibition in primary rat hepatocytes. My data support a model by which AKT rapidly promotes glucose contribution to glycogen synthesis by increasing glucose phosphorylation. I also sought to address how early activation of AKT affects glucose metabolism in vivo. Using transgenic mouse models, I investigated AKT posttranslational regulation of a key glycolytic regulator, PFKFB2, and how it affected whole-body glucose homeostasis. Together, my thesis introduces a non-canonical mechanism by which AKT signaling regulates glucose utilization in the liver, and points to new avenues of inquiry for understanding hepatic glucose flux

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Titchenell, Paul M.; Baur, Joseph A. Committee members: Arany, Zoltan P.; Marks, Michael S.; Wells, Rebecca G.; Wellen, Kathryn E.

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247973201

Access Restriction:

Restricted for use by site license