Life Sciences Commons^™

Functional And Skeletal Muscle Impairments In Progressive Diabetic Ckd, Daniel Bittel

Arts & Sciences Electronic Theses and Dissertations

1-in-3 persons with type 2 diabetes (T2DM) develop chronic kidney disease (CKD), which is characterized by progressive renal dysfunction leading to end-stage renal disease. In response to elevated blood glucose and systemic inflammation of diabetes, a process of active thickening of the renal glomerular basement membrane ensues with concomitant damage to the structural supports (podocytes) of the kidneyճ filtration barrier. This results in impaired renal filtration. The metabolic sequelea of T2DM and CKD also, synergistically, alter skeletal muscleճ degradative pathways, satellite cell function (muscle reparative cells), and mitochondrial health (muscle energetic machinery) -- resulting in muscle breakdown, poor muscle quality, …

Role Of Eps15 Homology Domain-Containing Protein 4 (Ehd4) In The Kidney, Shamma Rahman

Theses & Dissertations

In the kidney, endocytic recycling regulates the abundance of channels and transporters in the membrane of the tubular epithelium, and thereby controls the kidney’s ability to regulate water homeostasis. In recent years, a family of proteins called Eps15 homology domain-containing (EHD) proteins has emerged as important regulators of the endocytic recycling pathway. Mammals express four paralogs of EHD proteins, EHD1-4, that are expressed in different tissues. Although EHD4 is expressed in the kidney, the specific physiological role of EHD4 in the kidney remains unknown. Therefore, this dissertation was focused to elucidate the physiological role of EHD4 in the kidney. In …

Mechanisms For The Potassium Sparing Effects Of Furosemide In Mice On High Potassium Diets, Bangchen Wang

Theses & Dissertations

Because of its cardio-protective benefits, diets that are low in Na⁺ and high in K⁺ are often warranted in conjunction with use of diuretics such as furosemide for treating hypertension. It is critical to understand how such diets influence the diuretic actions on renal K⁺ handling in order to choose the best drug for patients.

Furosemide is a commonly used K-wasting diuretic. It increases urinary K⁺ excretion by increasing distal Na⁺ delivery that stimulates K⁺ secretion. However, in wild-type mice (WT) adapted to an alkaline low Na⁺ high K⁺ diet (LNaHK), both …

Functional Changes Associated With Shroom3 Deficiency And Mutation: Implications In Renal Pathophysiology And Disease, Doyun Ko

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) is a substantial global health burden that has recently been linked to the genetic locus SHROOM3 by several genome-wide association studies. Shroom3 is an actin-binding protein that is necessary for inducing apical constriction in epithelial cells. Our lab has previously shown that Shroom3 is critical for proper kidney development and loss of Shroom3 produces symptoms associated with CKD. As hypertension is both a leading cause and comorbidity of CKD, I hypothesized that loss of Shroom3 confers increased susceptibility to hypertension. Using a high-salt induced model of hypertension, I show that Shroom3 deficient mice do not become …

The Role Of Alström Syndrome 1 (Alms1) In Hypertension, Salt Sensitivity And Metabolic Syndrome, Keyona Nicole King-Medina

Wayne State University Dissertations

In humans, inactivating mutations in the Alström syndrome 1 (ALMS1) gene cause obesity, insulin resistance and hypertension (metabolic syndrome). More so, SNPs in the ALMS1 gene have been associated with kidney disease and cardiovascular disease. The

mechanisms causing these alterations are unclear. We recently found that the ALMS1 is expressed in the kidney thick ascending limb (TAL) where it mediates endocytosis of the renal Na/K/2Cl cotransporter termed NKCC2. To study the role of ALMS1 in renal

physiology we generated ALMS1 knockout (KO) rats in a Dahl salt-sensitive genetic background via zinc-finger nuclease targeting. We previously found that the amount of …