The Co-Existence of Insulin-Mediated Decreased Mean Arterial Pressure and Increased Sympathetic Nerve Activity is not Mediated by the Baroreceptor Reflex and Differentially By Hypoglycemia

Lu, Huiqing; Duanmu, Zhengbo; Scislo, Tadeusz J.; Dunbar, Joseph C.

doi:10.3109/10641969809053213

Cited by 18 publications

(16 citation statements)

References 19 publications

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“…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].…”

Section: Discussionsupporting

confidence: 91%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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Disparity of autonomic control in type 2 diabetes mellitus

et al. 2004

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Aims/hypothesis: Acute insulinaemia activates the sympathetic drive in a nonuniform manner. The extent and nature of such activation in type 2 diabetic patients who do not have neuropathy have not yet been addressed despite evidence relating sympathetic activation to cardiovascular risk. We planned to determine the magnitude and extent of the sympathetic drive and its reflex responses in patients with type 2 diabetes and fasting hyperinsulinaemia. Methods: We measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multiunit bursts and single unit muscle sympathetic nerve activity (s-MSNA) in 17 overweight patients with type 2 diabetes and two matched normal control groups comprising 17 overweight and 16 normal-weight subjects. We also tested the MSNA and s-MSNA responses to cold pressor and isometric hand-grip tests, along with the effect of sympatho-vagal balance on heart period variability. Results: Both MSNA and s-MSNA in the group with type 2 diabetes (66±3.5 bursts/100 beats and 78±4.5 impulses/100 beats) were greater (at least p<0.0001) than in the overweight control group (42±2.6 bursts/100 beats and 48±3.4 impulses/100 beats) and normal-weight control group (43±6.2 bursts/100 beats and 51±7.1 impulses/100 beats), though the three groups had similar reflex responses, baroreflex sensitivity and sympathovagal balance controlling the heart period. Conclusions/ interpretation: The patients with type 2 diabetes had no evidence of impaired reflex or autonomic control of heart period variability at a time when there was central sympathetic activation to the periphery. Furthermore, being overweight itself was not associated with sympathetic activation.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Disparity of autonomic control in type 2 diabetes mellitus

et al. 2004

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“…Previous studies have demonstrated increased sympathetic traffic to lumbar and renal (8) and adrenal nerves (9) in response to acute hypoglycemia. Insulin-induced hypoglycemia has also been shown to increase plasma norepinephrine after adrenalectomy, consistent with sym- pathoexcitation and catecholamine release from peripheral nerves (16).…”

Section: Discussionmentioning

confidence: 99%

“…Hoffman et al (7) found that skeletal muscle SNA in type 1 diabetic and nondiabetic human subjects increased during insulin-induced hypoglycemia above that observed during euglycemia at the same insulin infusion rate. Lu et al (8) reported that renal SNA in anesthetized rats exposed to insulinmediated hypoglycemia increased above that observed for hyperinsulinemia with maintained euglycemia. Further, Carlsson et al (9) found that acute insulin-induced hypoglycemia as well as 2-deoxy-D-glucose administration (which induces central neuroglycopenia) increase sympathetic adrenal nerve traffic in anesthetized rats.…”

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confidence: 99%

Effect of Acute and Antecedent Hypoglycemia on Sympathetic Neural Activity and Catecholamine Responsiveness in Normal Rats

Sivitz

Herlein

Morgan³

et al. 2001

Diabetes

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Adrenergic responsiveness to acute hypoglycemia is impaired after prior episodes of hypoglycemia. Although circulating epinephrine responses are blunted, associated alterations in adrenal sympathetic nerve activity (SNA) have not been reported. We examined adrenal nerve traffic in normal conscious rats exposed to acute insulin-induced hypoglycemia compared with insulin with (clamped) euglycemia. We also examined adrenal SNA and catecholamine responses to insulin-induced hypoglycemia in normal conscious rats after two antecedent episodes of hypoglycemia (days ؊2 and ؊1) compared with prior episodes of sham treatment. Acute insulin-induced hypoglycemia increased adrenal sympathetic nerve traffic compared with insulin administration with clamped euglycemia (165 ؎ 12 vs. 118 ؎ 21 spikes/s [P < 0.05]; or to 138 ؎ 8 vs. 114 ؎ 10% of baseline [P < 0.05]). In additional experiments, 2 days of antecedent hypoglycemia (days -2 and -1) compared with sham treatment significantly enhanced baseline adrenal SNA measured immediately before subsequent acute hypoglycemia on day 0 (180 ؎ 11 vs. 130 ؎ 12 spikes/s, respectively; P < 0.005) and during subsequent acute hypoglycemia (229 ؎ 17 vs. 171 ؎ 16 spikes/s; P < 0.05). However, antecedent hypoglycemia resulted in a nonsignificant reduction in hypoglycemic responsiveness of adrenal SNA when expressed as percent increase over baseline (127 ؎ 5% vs. 140 ؎ 14% of baseline). Antecedent hypoglycemia, compared with sham treatment, resulted in diminished epinephrine responsiveness to subsequent hypoglycemia. Norepinephrine responses to hypoglycemia were not significantly altered by antecedent hypoglycemia. In summary, prior hypoglycemia in normal rats increased adrenal sympathetic tone, but impaired epinephrine responsiveness to acute hypoglycemia. Hence, these data raise the intriguing possibility that increased sympathetic tone resulting from antecedent hypoglycemia downregulates subsequent epinephrine responsiveness to hypoglycemia. Alternatively, it is possible that the decrease in epinephrine responsiveness after antecedent hypoglycemia could be the result of reduced adrenal sympathetic nerve responsiveness. Diabetes 50:1119 -1125, 2001 I mpaired hypoglycemic counterregulation and hypoglycemia unawareness are well-recognized complications of long-standing diabetes (1,2). Hypoglycemia unawareness has also been observed as a reversible consequence of transient prior hypoglycemic events (3-5) and has been observed even in individuals without diabetes (6). However, the pathophysiology of hypoglycemic counterregulation and hypoglycemia unawareness is still unclear. Although much has been learned of catecholamine and other hormonal responses to hypoglycemia, the role of sympathetic neural activity per se to adrenal and other tissues has received only limited study.Peripheral sympathetic nerve activity (SNA) originating in hypothalamic centers may be important in the counterregulatory response to hypoglycemia. Hoffman et al. (7) found that skeletal muscle SNA in type 1 diabetic and nondia...

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“…For instance, the insulin-induced vasodilatation has been reported to be widespread [1, 4], and includes femoral, carotid and coronary vascular beds [5, 6, 7, 8, 9]. The activation of sympathetic output has been found to affect the lumbar region more than adrenal or renal regions [2, 10, 11, 12]. Recently, it has been shown in anesthetized pigs that insulin infusion caused an increase in renal blood flow which was the net result of a vasoconstriction involving sympathetic α-adrenoceptor-mediated mechanisms and a predominant vasodilatation which involved the endothelial release of nitric oxide [13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Insulin on Coronary Blood Flow in Anesthetized Pigs

Molinari

Battaglia²,

Grossini³

et al. 2002

J Vasc Res

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Insulin can influence the vasculature by a sympathetically mediated vasoconstriction and a vasodilatation; the latter effect predominates in the renal circulation of anesthetized pigs. We determined the effect of intravenous infusion of insulin on coronary blood flow in pentobarbitone-anesthetized pigs at constant heart rate, arterial pressure and blood levels of glucose and potassium. In 6 pigs, infusion of 0.004 IU kg^–1 min^–1 of insulin decreased coronary flow despite increasing left ventricular dP dt_max^–1; when the latter was abolished by propranolol, the coronary flow response was augmented. The mechanisms of this response were examined in 22 pigs given propranolol. Phentolamine changed coronary flow response to an increase (6 pigs) and this was abolished by intracoronary injection of N^ω-nitro-L-arginine methyl ester (L-NAME; 5 pigs). L-NAME augmented coronary flow response (6 pigs) and this was abolished by phentolamine (5 pigs). In 18 pigs given propranolol, three incremental doses of insulin caused graded coronary flow decreases whether L-NAME was given (6 pigs) or not (6 pigs) beforehand, and caused graded coronary flow increases after phentolamine (6 pigs). Thus insulin caused a coronary vasoconstriction mediated by sympathetic α-adrenergic effects and a vasodilatation related to the release of nitric oxide. The net effect was a coronary vasoconstriction.

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The Co-Existence of Insulin-Mediated Decreased Mean Arterial Pressure and Increased Sympathetic Nerve Activity is not Mediated by the Baroreceptor Reflex and Differentially By Hypoglycemia

Cited by 18 publications

References 19 publications

Disparity of autonomic control in type 2 diabetes mellitus

Disparity of autonomic control in type 2 diabetes mellitus

Effect of Acute and Antecedent Hypoglycemia on Sympathetic Neural Activity and Catecholamine Responsiveness in Normal Rats

Effects of Insulin on Coronary Blood Flow in Anesthetized Pigs

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