The sympathetic response to euglycaemic hyperinsulinaemia

Abstract

Summary. Sympathetic nervous system activation by insulin has been suggested as a mechanism explaining the association between insulin resistance and hypertension. We further examined the effect of insulin by direct microneurographic muscle and skin nerve sympathetic activity recordings during euglycaemic insulin clamps in healthy subjects. The mean plasma insulin level was elevated from 5.3 + 0.7 to 92.2 + 2.2 mU/1 in seven subjects during a 90-min one-step clamp. In six other subjects plasma insulin was further raised from 85.7 _+ 4.0 mU/1 to 747 + 53 mU/1 between 45-90 min (two-step clamp). Four of the latter subjects received a sham clamp with NaC1 infusions only on a second recording session. At the low dose of insulin muscle nerve sympathetic activity increased from a resting level of 22.7 + 5.0 bursts per min to 27.7 + 5.0 bursts per rain at 15 min (p < 0.05). The increases in muscle nerve sympathetic activity were significant (p < 0.001; ANOVA) throughout insulin infusion, with a slight further increase (from 29.2 + 1.6 to 32.3 + 1.9 bursts per min) at the supraphysiological insulin concentration. During sham clamps muscle nerve sympathetic activity did not increase. Both insulin clamps induced minor, but significant, increases in forearm venous plasma noradrenaline concentrations. Skin nerve sympathetic activity (n = 3) did not change during insulin infusions. Heart rate increased slightly but significantly (p < 0.005), during the insulin damps. Blood pressure was not notably affected. In conclusion, hyperinsulinaemia was associated with increased vasoconstrictor nerve activity to skeletal muscle and with no change of sympathetic outflow to skin.

The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension.

“…Despite this sympathetic excitation, forearm vascular resistance fell and mean arterial pressure did not rise. Berne et al 21 also reported that insulin increased muscle sympathetic nerve activity and plasma norepinephrine without significant changes in arterial pressure.…”

“…Morgan and colleagues have reported that hyperinsulinemia increased lumbar sympathetic nerve activity but not renal or adrenal sympathetic nerve activity in normotensive Sprague-Dawley (unpublished observations) or WistarKyoto rats. 32 In humans, Berne et al 21 have reported that hyperinsulinemic clamp increases sympathetic nerve activity to muscle but not to skin.…”

“…- 21 In addition, hyperinsulinemia increases norepinephrine turnover in rats. 8 Interestingly, there is a striking regional nonuniformity in the sympathetic nerve activity responses to insulin.…”

Physical Activity and Low‐Fat Diet: Is it Enough to Maintain Weight Stability in the Reduced‐Obese Individual Following Weight Loss by Drug Therapy and Energy Restriction?

“…Because these factors have been shown to increase energy expenditure (EE) and reduce energy intake (EI) (9)(10)(11)(12)(13), their decrease with fat loss is certainly detrimental to the maintenance of weight stability in the reduced-obese state. Because fat oxidation seems to be dependent upon P-adrenergic stimulation (14,15), the decrease in SNS activity is especially problematic in the context that obese and formerly obese individuals seem to have a preference for this macronutrient (1 6,17).…”

Relationship Between Hunger‐Satiety Feelings and Various Metabolic Parameters in Women with Obesity During Controlled Weight Loss

“…The liver (12), the autonomic nervous system (19), and the hypothalamus (10, II) have been proposed as sites of the anorexic action of insulin. Although there is evidence that insulin increases sympathetic nervous activity (20)(21)(22), the connection to appetite suppression remains hypothetical. Recent experiments with the ob gene have demonstrated increased ob gene expression in adipose tissue after insulin injection in rats, which would represent another peripheral action of insulin (23).…”