The progression from mild to severe hyperglycemia coupled with insulin resistance causes mitochondrial dysfunction and alters the metabolic secretome of epithelial kidney cells

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Braga, PC (Author) Other; Bernardino, RL (Author) ICBAS; Guerra-Carvalho, B (Author) Other; Carrageta, DF (Author) Other; Oliveira, PF (Author) Other; Rodrigues, AS (Author) Other; Alves, MG (Author) Other

Journal

Title: Experimental Cell Research

Vol. 431

ISSN: 0014-4827

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00Y-YBA

DOI: 10.1016/j.yexcr.2023.113744

Abstract (EN): Diabetic nephropathy (DN) and insulin resistance (IR) in kidney cells are considered main causes for end-stage renal failure. However, it is unclear how IR affects early stages of the disease. Here, we investigate the impact of mild (11 mM) and severe (22 mM) hyperglycemia, with and without induced IR, on cellular metabolism and mitochondrial bioenergetics in a human kidney cell line (HK-2). IR in HK-2 cells was induced with palmitic acid and cellular cytotoxicity was studied. We evaluated the impact of mild and severe hyperglycemia with and without IR on the metabolic secretome of the cells, their live-cell mitochondria function, mitochondrial membrane potential, and mitochondrial complex activities. Furthermore, we measured fatty acid oxidation and lipid accumulation. Cells cultured under mild hyperglycemic conditions exhibited increased mitochondrial bioenergetic parameters, such as basal respiration, ATP-linked production, maximal respiration capacity, and spare respiration capacity. However, these parameters decreased when cells were cultured under higher glucose concentrations when IR was induced. Our data suggests that progression from mild to severe hyperglycemia induces a metabolic shift, where gluconeogenic amino acids play a crucial role in supplying the energy requirements of HK-2. To our knowledge, this is the first study to evaluate the progression from mild to severe hyperglycemia allied to IR in human kidney cells. This work highlights that this progression leads to mitochondrial dysfunction and alters the metabolic profile of kidney cells. These results identify possible targets for early intervention in DN.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14