Recently, at the Annual Meeting of the Chinese Diabetes Society (CDS), Professor Zhu Zhiming from the Department of Hypertension and Endocrinology, Daping Hospital, Army Medical University, delivered a systematic and in-depth lecture on the regulatory mechanisms of salt metabolism under diabetic conditions.
The homeostasis of body salt metabolism relies on the coordinated regulation of multiple systems and organs, including intestinal salt absorption, renal salt excretion, salt exchange between interstitial fluid and body fluids, salt excretion through skin sweating, and modulation of intake behavior by the salt taste system.Related molecular pathways involve ion channels or transporters such as CFTR, SGLT1, Na⁺/H⁺ exchanger, ENaC, TRPV1, TRPM5, TRPA1, TRPV4, and Piezo channels.
The pathogenesis of diabetes-associated hypertension is closely related to salt sensitivity.Insulin resistance is commonly observed in salt-sensitive animal models, and diabetic patients show a significantly enhanced blood pressure response to high-salt load, indicating that the diabetic state itself markedly amplifies the effect of salt on blood pressure.
Sodium-glucose cotransporters (SGLTs) play a key role in this process, especially SGLT2 expressed in the kidney. As an important molecular hub for coupled glucose and sodium transport, SGLT2 serves as a core link connecting glucose control and sodium-water balance.
Both clinical and experimental data demonstrate that in diabetic patients with poor glycemic control, urinary sodium excretion is significantly decreased, and blood glucose level is negatively correlated with urinary sodium excretion.This difference disappears when blood glucose is improved.
Animal studies further reveal that in obese diabetic mice, a high-salt diet not only significantly elevates blood pressure but also reduces urine volume and urinary sodium excretion, suggesting that a high-salt load under diabetic conditions tends to promote sodium and water retention rather than sodium excretion.
High salt exhibits abnormal regulation of renal SGLT2 expression in the diabetic state.Experimental studies show that in diabetic models, high salt inhibits renal SGLT2 expression, leading to reduced urinary sodium and glucose excretion, whereas this effect is not significant in normal controls.
Under normal conditions, high salt can activate PPARδ in adipose tissue, promote adiponectin production, thereby inhibiting SGLT2 and enhancing urinary sodium and glucose excretion.However, in diabetes, the PPARδ–adiponectin–SGLT2 axis is dysfunctional, resulting in the loss of this protective mechanism.
In conclusion, SGLTs are key molecules linking the homeostatic regulation of salt and glucose in the body.In diabetes, dysfunction of the renal PPARδ–adiponectin–SGLT2 axis leads to sodium and water retention, thereby promoting the development and progression of hypertension.