Chronic activation of the sympathetic nervous system may be a pathogenetic mechanism by which hyperinsulinemia induces cardiovascular damage in insulin-resistant NIDDM patients. The influence of physiological hyperinsulinemia (∼ 700 pmol/l) on basal and stimulated sympathetic outflow was studied in 12 lean normotensive subjects with well-controlled NIDDM without complications and in 13 matched control subjects. Forearm blood flow (FBF) was measured with forearm plethysmography; sympathetic nervous system activity was assessed by the [3H]norepinephrine (NE) tracer method. NIDDM patients were insulin resistant (glucose infusion rates 31.8 ± 3.8 vs. 48.7 ± 2.0 mumol·kg−1 · min−1 in control subjects, P < 0.01). After a mixed meal, NIDDM patients showed a hyperinsulinemic response (2-h insulin levels: NIDDM patients 324 ± 34 pmol/l, control subjects 165 ± 19 pmol/l, P < 0.001). Insulin infusion induced a vasodilator response (not significantly different between the groups). Arterial plasma NE levels and total-body NE spillover increased significantly (total spillover in NIDDM patients from 0.77 ± 0.09 to 1.18 ± 0.16 nmol · m−2 · min−1, in control subjects from 0.98 ± 0.14 to 1.23 ± 0.18 nmol · m−2 · min−1 P < 0.01 for all, not different between groups). Total-body NE clearance did not change. Sympathetic stimulation (lower-body negative pressure [LBNP] 15 mmHg) induced forearm vasoconstriction and increased arterial and venous plasma NE and total NE spillover. Responses of FBF and NE kinetics to LBNP were not significantly different between groups and were not altered by hyperinsulinemia. Although these nonobese subjects with uncomplicated NIDDM showed postprandial hyperinsulinemia and resistance to the effect of insulin on glucose metabolism, this group was not resistant to the vasodilator and sympathetic stimulant effects of insulin. Responses to sympathetic stimuli (LBNP) were normal and unaffected by physiological hyperinsulinemia. Therefore, because of daily life hyperinsulinemia, chronic sympathetic stimulation could be operative in these patients and may explain the increased incidence of hypertension and/or cardiovascular complications.
Effects of Insulin on Vascular Tone and Sympathetic Nervous System in NIDDM
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Cees J J Tack, Paul Smits, Jacques J Willemsen, Jacques W M Lenders, Theo Thien, Jos A Lutterman; Effects of Insulin on Vascular Tone and Sympathetic Nervous System in NIDDM. Diabetes 1 January 1996; 45 (1): 15–22. https://doi.org/10.2337/diab.45.1.15
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