Mechanisms of Insulin Action on Sympathetic Nerve Activity

Disparity of autonomic control in type 2 diabetes mellitus

“…Our new findings are consistent with those in a large number of reports in experimental animals and normal humans showing that an increase in plasma insulin levels causes a nonuniform activation of the sympathetic drive [1][2][3][4][5][6][7][8][9][10][11][12]. For instance, in experimental animals, administration of insulin into the cerebral ventricles or intravenously has been shown to increase sympathetic nerve activity in efferent lumbar nerves without affecting efferent renal or adrenal nerves [6,7]. Similarly in normal humans, acute hyperinsulinaemia with euglycaemic clamp increased the sympathetic drive to the forearm and not to the adrenomedullary region [8].…”

“…This has been shown using techniques such as venous plasma catecholamine concentration [2] and total body and forearm norepinephrine spillover [3] as well as by direct neural recordings [4,5]. Experiments involving direct measurement of regional sympathetic nerve activity in animal studies have shown that central and systemic insulinaemia cause preferential stimulation of lumbar but not renal or adrenal regions [6,7]. In normal humans and those with insulin resistance it has also been shown that insulinaemia causes nonuniform regional sympathetic activation, with reports showing an increase in output to the forearm and legs but not to the kidneys [8,9].…”

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease

“…Sympathetic overactivity and insulin resistance, and therefore the consequences of insulin resistance including hyperglycaemia, are clearly linked, but the causal direction of that association is uncertain, since insulin may act on the central nervous system to increase sympathetic outflow; alternatively, an increase in sympathetic activity could itself result in insulin resistance [40]. Our cross-sectional study cannot determine the direction of causality, as abnormalities in cardiovascular risk factors and autonomic function will, of necessity, be established in this older age group.…”

Baroreceptor sensitivity and diabetes mellitus

“…Also both essential hypertension and type 2 DM exert a combined synergistic effect that diminishes BRS [59]. Hypertension in diabetic patients has also been attributed to the actions of hyperinsulinemia in stimulating the sympathetic nervous system [61,65]. -Renal damage as evidenced by microalbuminuria: In microalbuminuric type 1 DM patients, BRS was found to be depressed [66].…”

“…-Insulin resistance/hyperinsulinemia: Studies show that DM patients with insulin resistance/hyperinsulinemia have a reduced BRS [54,[58][59][60]. This association can perhaps be explained by the findings that insulin causes sympathetic nervous system activation [61,62]. -Essential hypertension [59]: Hypertension occurs more often in diabetic patients (especially in type 2 DM) than in nondiabetic patients with most hypertensive diabetic patients having essential hypertension [63].…”