To detect the changes in the liver function in both male and female OVE26 mice from young to adults for better understanding of type 1 diabetes-induced hepatic changes, OVE26 mice and wild-type FVB mice were raised in the same environment without any intervention, and then killed at 4, 12, 24 and 36 weeks for examining liver's general properties, including pathogenic and molecular changes. The influence of diabetes on the bodyweight of male and female mice was different. Both male and female OVE26 mice did not obtain serious liver injury or non-alcoholic fatty liver disease, manifested by mild elevation of plasma alanine transaminase, and less liver lipid content along with significantly suppressed lipid synthesis. Uncontrolled diabetes also did not cause hepatic glycogen accumulation in OVE26 mice after 4 weeks. Oxidative stress test showed no change in lipid peroxidation, but increased protein oxidation. Changed endoplasmic reticulum stress and apoptosis along with increased antioxidant capacity was observed in OVE26 mice. In conclusion, uncontrolled type 1 diabetes did not cause hepatic lipid deposition most likely because of reduced lipids synthesis in response to insulin deficiency. Enhanced antioxidant capacity might not only prevent the occurrence of severe acute liver injury but also the self-renewal, leading to liver dysfunction.
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http://dx.doi.org/10.1111/jcmm.14504 | DOI Listing |
Mol Ther
September 2024
Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:
Transforming growth factor (TGF)-β signaling is a well-established pathogenic mediator of diabetic kidney disease (DKD). However, owing to its pleiotropic actions, its systemic blockade is not therapeutically optimal. The expression of TGF-β signaling regulators can substantially influence TGF-β's effects in a cell- or context-specific manner.
View Article and Find Full Text PDFInt J Mol Sci
March 2023
Chronic Disease Program, Kidney Research Centre, Ottawa Hospital Research Institute, Ottawa, ON K1H 8M5, Canada.
Hypertension and diabetes induce vascular injury through processes that are not fully understood. Changes in extracellular vesicle (EV) composition could provide novel insights. Here, we examined the protein composition of circulating EVs from hypertensive, diabetic and healthy mice.
View Article and Find Full Text PDFKidney Int
December 2022
Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Renal Program, James J Peters VA Medical Center at Bronx, Bronx, New York, USA. Electronic address:
The pathogenesis of diabetic kidney disease (DKD) involves multifactorial processes that converge to initiate and advance the disease. Although DKD is not typically classified as an inflammatory glomerular disease, mounting evidence supports the involvement of kidney inflammation as a key contributor in DKD pathogenesis, particularly through macrophages. However, detailed identification and corresponding phenotypic changes of macrophages in DKD remain poorly understood.
View Article and Find Full Text PDFNeuropathology
February 2023
Department of Human Physiology and Pathophysiology, University of Warmia and Mazury in Olsztyn, School of Medicine, Collegium Medicum, Olsztyn, Poland.
Type 1 diabetes (T1D) may affect the peripheral nervous system and alter the expression of proteins contributing to inflammation and cellular cytoskeleton dysfunction, in most cases leading to the development of diabetic length-dependent neuropathy (DLDN). In the present study, we performed immunohistochemistry (IHC) to probe the expression of the receptor for advanced glycation end products (RAGE); its key ligands, high-mobility group box 1 (HMGB1), S100 calcium-binding protein B (S100B), and carboxymethyl-lysine (CML - advanced glycation end products (AGE)); and its cytoplasmic tail-binding partner, diaphanous related formin 1 (DIAPH1) and associated molecules, beta-actin (ACTB) and profilin 1 (PFN1) proteins in sciatic nerves harvested from seven-month old FVB/OVE26 mice with genetically-mediated T1D. We found that the amount of RAGE, HMGB1, and S100B proteins was elevated in diabetic vs the non-diabetic groups, while the amount of DIAPH1, ACTB, as well as PFN1 proteins did not differ between these groups.
View Article and Find Full Text PDFLife Sci
December 2021
Department of Medicine, Division Nephrology, University of Louisville, Louisville, KY 40292, USA; Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA. Electronic address:
Aims: Transforming growth factor-β (TGF-β) mediates fibrotic manifestations of diabetic nephropathy. We demonstrated proteasomal degradation of anti-fibrotic protein, nuclear factor-erythroid derived 2 (NF-E2), in TGF-β treated human renal proximal tubule (HK-11) cells and in diabetic mouse kidneys. The current study examined the role of mitogen-activated protein kinase (MAPK) pathways in mediating NF-E2 proteasomal degradation and stimulating profibrotic signaling in HK-11 cells.
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