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Dietary sodium restriction decreases insulin secretion without affecting insulin sensitivity in humans
James M Luther1, Loretta M Byrne, Chang Yu
1Divisions of Clinical Pharmacology, Department of Medicine (J.M.L., L.M.B., N.J.B.), Nephrology and Hypertension (J.M.L.), and Cardiovascular Medicine (T.J.W.), and Departments of Biostatistics (C.Y.) and Pharmacology (J.M.L.), Vanderbilt University Medical Center, Nashville, Tennessee 37232-6602.
Context:
Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear.
Objective:
To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans.
Design:
We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet.
Setting:
Academic clinical research center.
Participants:
Healthy, nondiabetic, normotensive volunteers.
Interventions:
Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5-7 days.
Main Outcome Measures:
Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle.
Results:
A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (-16.0 ± 5.6%; P = .007) and C-peptide responses (-21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (-1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion.
Conclusions:
Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity.
Insights
Low dietary sodium intake significantly reduces insulin and C-peptide secretion in humans. This effect occurs independently of changes in insulin sensitivity, highlighting a novel mechanism impacting glucose metabolism.
Area of Science:
- Endocrinology
- Metabolic Research
- Human Physiology
Background:
- The renin-angiotensin-aldosterone system (RAAS) plays a role in preventing diabetes in high-risk individuals, but the precise mechanism is not fully understood.
- Investigating the impact of RAAS activation on insulin secretion is crucial for understanding glucose homeostasis and diabetes development.
Purpose of the Study:
- To test the hypothesis that activation of the endogenous RAAS or exogenous aldosterone impairs insulin secretion in humans.
- To elucidate the role of dietary sodium intake in modulating insulin secretion and sensitivity.
Main Methods:
- A randomized, blinded crossover study design was employed, comparing aldosterone infusion versus vehicle control.
- Participants underwent dietary interventions with either low-sodium (20 mmol/d) or high-sodium (160 mmol/d) intake for 5-7 days.
- Acute insulin secretory response was assessed using hyperglycemic clamps under controlled sodium balance.
Main Results:
- A low-sodium diet led to increased endogenous aldosterone and plasma renin activity.
- The acute glucose-stimulated insulin response decreased by 16.0% (P = .007) and C-peptide response by 21.8% (P = .014) during low sodium intake.
- Exogenous aldosterone infusion did not significantly alter acute insulin response or insulin sensitivity index.
Conclusions:
- Low dietary sodium intake demonstrably reduces insulin secretion in humans.
- This reduction in insulin secretion is independent of changes in insulin sensitivity.
- Findings suggest a direct effect of sodium balance on pancreatic beta-cell function.
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