Disrupted Renal Clock and Blood Pressure Rhythms in Type 2 Diabetic Nephropathy

🎖️ Top 10% JournalJan 19, 2026Clinical science (London, England : 1979)

Disrupted Kidney Daily Rhythms and Blood Pressure Patterns in Type 2 Diabetic Kidney Disease

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Abstract

T2DN rats displayed impaired circadian rhythms in blood pressure measurements, with significant alterations in circadian-related gene expression.

Type 2 diabetes mellitus is a major risk factor for diabetic kidney disease.
T2DN rats showed disrupted circadian rhythms specifically in mean arterial pressure and systolic blood pressure.
Heart and locomotor activity in T2DN rats maintained their rhythmic patterns despite the disruption in blood pressure rhythms.
Transcriptomic analysis indicated altered expression of circadian genes, including Per1, which may be linked to insulin sensitivity and lipid metabolism.
Neither renal denervation nor melatonin treatment successfully restored normal circadian rhythms in T2DN rats.

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Type 2 diabetes mellitus (T2DM), accounting for approximately 90% of adult-onset diabetes cases, is a major risk factor for diabetic kidney disease (DKD). Emerging evidence has linked T2DM with disrupted circadian rhythms. However, its role in the progression of DKD remains poorly understood. To investigate the relationship between circadian rhythms and DKD, we used the type 2 diabetic nephropathy (T2DN) rat, a non-obese model that replicates key features of human DKD. Circadian rhythms were assessed in both male and female T2DN rats at 20 and >35 weeks (young and old) by continuous measurements of mean arterial pressure (MAP), systolic blood pressure (SBP), heart and locomotor activity. Differential expression of circadian genes was evaluated by RNA-sequencing of kidney cortex. In separate cohorts, the effects of renal denervation and melatonin treatment on circadian parameters were examined. T2DN rats exhibited impaired circadian rhythms in MAP and SBP, while heart and locomotor activity retained rhythmicity. Transcriptomic analysis revealed altered expression of several circadian-related genes, including core circadian gene Per1 and multiple circadian-controlled genes involved in insulin sensitivity, lipid metabolism, and immune regulation between different groups of T2DN rats. Neither renal denervation nor melatonin administration restored normal circadian rhythms of T2DN rats. Our data suggest that circadian rhythm disruption of blood pressure is a consistent feature of T2DN rats, and that targeting circadian clock components such as Per1 could offer potential therapeutic strategies.

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