Hyperinsulinemia rather than insulin resistance itself induces blood pressure elevation in high fat diet-fed rats

ABSTRACT

Objective

To investigate if insulin resistance per se or the accompanying hyperinsulinemia induced hypertension and its underlying mechanisms.

Methods

Sprague-Dawley rats were randomized into normal diet-fed group (ND group) and high-fat diet-fed group (HFD group). Then, the HFD group was further randomly divided into the control group (HFD_C group), the PIO group (treated with pioglitazone), the STZ_DM group (to induce diabetes with streptozotocin) and the DM+Ins group (streptozotocin injection followed by insulin treatment). Insulin sensitivity, plasma insulin, endothelin-1, norepinephrine, aldosterone, angiotensinⅡ and 24-h urinary sodium excretion (USE) levels of the groups were measured and analyzed. A multiple stepwise regression analysis method was applied to exam our hypothesis.

Results

Compared to HFD_C group, the groups with lower plasma insulin, the PIO group and STZ_DM group, showed higher USE and lower blood pressure. The groups with higher plasma insulin (but same level of insulin resistance), the HFD_C group and DM+Ins group, showed lower USE and higher blood pressure. The 24-h urinary sodium excretion was the most important contributor to the significant changes of blood pressure with an R² of 25.2% in this animal experiment.

Conclusions

It is the compensatory hyperinsulinemia rather than insulin resistance per se that causes blood pressure elevation. The urinary sodium excretion is the key mediator among the multiple mechanisms. Therapies targeting hyperinsulinemia and restricting salt intake may favor a better control of hypertension associated with insulin resistance.

KEYWORDS:

• Blood pressure
• hyperinsulinemia
• insulin resistance
• urinary sodium excretion
• animal experiment

Acknowledgments

This work was supported by the generous research grants from the Clinical Research Institute of China-Japan Friendship Hospital.

Declaration of interest statement

The authors declare that they have no conflict of interest.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

None.