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Full-Text Articles in Biochemical Phenomena, Metabolism, and Nutrition

Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow Jul 2026

Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow

MUSC Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest five-year survival rates among cancers and is characterized by near-ubiquitous occurrence of oncogenic KRAS mutations. Oncogenic KRAS activates several downstream pathways, including ERK 1/2 MAPK and PI3K, which are critical for PDAC. However, accumulating evidence suggests that PI3K activity can be maintained independent of oncogenic KRAS. The high prevalence of KRASG12R in PDAC challenges the prevailing model of KRAS-driven PI3K activation, as this mutant is defective in direct engagement with PI3Kα. These observations raise important questions regarding how PI3K signaling is sustained in PDAC. Here, we investigated KRAS-independent mechanisms that …


Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler Jan 2026

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …


Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca Apr 2025

Zonal Hepatocellular Responses To Acute Ethanol: Impacts On Mitochondrial Function And Metabolism, Matthew T. Savoca

MUSC Theses and Dissertations

Background: Ethanol (EtOH) consumption causes hepatocellular mitochondrial depolarization (mtDepo) and mitophagy. Here, the Aims were to develop techniques to characterize sublobular hepatocellular metabolism and the distribution of mtDepo and mitophagy after acute EtOH. Methods: Wildtype and GFP-LC3 transgenic mice were treated with EtOH or vehicle and administered the covalently labeling mitochondrial membrane potential (ΔΨ) reporter, MitoTracker Red (MTR), and/or the non-covalent ΔΨ reporter, rhodamine 123 (Rh123), prior to intravital imaging, liver fixation, or hepatocyte isolation. After in vivo MTR, hepatocytes were isolated and sorted. Enrichment in E-cadherin (ECAD) and cytochrome P4502E1 in periportal (PP) and pericentral (PC) hepatocytes, respectively, validated …


Metabolism Of Branched-Chain Amino Acids By Rat Skeletal Muscle: Regulation Of Branched-Chain Alpha-Keto Acid Dehydrogenase, Robert Paul Aftring Jan 1987

Metabolism Of Branched-Chain Amino Acids By Rat Skeletal Muscle: Regulation Of Branched-Chain Alpha-Keto Acid Dehydrogenase, Robert Paul Aftring

MUSC Theses and Dissertations

Catabolism of the essential branched-chain amino acids (BCAA) by skeletal muscle of the rat was investigated. In diaphragm muscles incubated in vitro oxidation and transamination of leucine or valine were accelerated by diabetes or starvation overnight. In the presence of pyruvate, transamination of BCAA by diaphragms was increased; oxidation of BCAA by diaphragms from diabetic or starved rats was increased by pyruvate but was inhibited in diaphragms of normal, fed rats. The effects on transamination were verified by direct measurements of the alpha-ketoisocaproate (KIC) product of leucine transamination. The effect of pyruvate on KIC oxidation by diaphragms was similar to …