Diabetes refers to a group of chronic diseases that affect the body’s ability to effectively utilize sugar, especially glucose, resulting in a buildup of sugar in the blood. The Centers for Disease Control and Prevention estimates that in 2022, 11.3% of the U.S. population will have diabetes, and 38% of adults age 18 and older and 49% of adults age 65 and older will have prediabetes, meaning their blood sugar levels are higher than normal. did. .

Komuraia Myakala

The long-term health effects of diabetes can be serious. Over time, diabetes can cause vision loss, nerve damage, and hearing loss, as well as affecting larger organ systems. In the United States, it is a major risk factor for cardiovascular and kidney disease. People with diabetes have an increased risk of high blood pressure, heart attack, and stroke. Additionally, one in three adults with diabetes has diabetic kidney disease (DKD).

In DKD, elevated glucose in the blood for a long period of time damages blood vessels and nephrons, the kidney cells responsible for filtering blood. DKD often occurs alongside other conditions such as high blood pressure, which can damage the kidneys over time. In recent research, biochemistry journal demonstrated the potential to alleviate this damage by improving the function of mitochondria, the organelles responsible for energy maintenance and production.

Komuraia Myakala, a research lecturer at Georgetown University, uses an animal model that mimics the progression of type 2 diabetes, known as the db/db mouse, to test hypotheses about DKD.

“To understand this disease, we need to choose the right model,” Myakala says. “All metabolic diseases are controlled by various signaling pathways. If there is a causal relationship to the progression of kidney disease, we need to understand the signaling proteins involved.”

Myakala et al/JBC

This immunofluorescence image shows kidney cells derived from the db/db (diabetic) mouse model. Filamentous actin, which is part of the cytoskeleton, is stained red to show the structure inside the cell. Macrophages, or immune cells, are green. In diabetic kidney disease, macrophages infiltrate the kidneys and secrete pro-inflammatory proteins and various elements that can cause damage over time.

During the study, db/db mice and healthy mice were given the supplement nicotinamide riboside (NR). NR, also known as vitamin B3, is a precursor to the biologically functional form of nicotinamide adenine nucleotide (NAD+) and can increase its levels in the body. A key coenzyme in metabolic processes, NAD+ is ubiquitous in all cell types and is essential for mitochondrial metabolism and cellular energy production.

The body naturally produces NAD+. Levels naturally decline with age, and diseases such as diabetes, cardiovascular disease, and neurological disorders can also cause a drop in NAD+.

“The pathogenesis of kidney disease between diabetes and aging is very different,” Myakala says. “Diabetes is usually a more severe form of kidney disease than when compared based on age alone.”

Inflammation is closely associated with mitochondrial damage and diabetic kidney disease. Feeding db/db mice with NR reduced inflammation and prevented many of the usual symptoms of decreased kidney function. For example, levels of blood protein markers, which increase with the progression of DKD, decreased after NR treatment.

This study helps demonstrate the importance of mitochondrial function in kidney disease, especially diabetes. Researchers still do not fully understand the mechanisms linking mitochondria and inflammatory diseases, and further research is needed. However, this study provides insight into the possibility of using supplementary NR to improve mitochondrial function and offers hope for DKD treatment.

Myakala describes his dedication to understanding the mechanisms of kidney disease as “unwavering.” He and his colleagues hope to continue his research to fill the gaps in understanding that exist between inflammation, mitochondria, and kidney disease.