Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat

Abstract

Somatosympathetic reflexes were studied in young hyperinsulinemic, insulin-resistant (Zucker fatty) rats (ZFR) and a related control (Zucker lean) strain (ZLR). Glucose metabolism was characterized by minimal model analysis of intravenous glucose tolerance test data. Seven-week-old ZFR (n ϭ 18) and ZLR (n ϭ 17) were studied under pentobarbital anesthesia. Mean body weight and plasma glucose and insulin concentration were significantly greater (P Ͻ 0.05) in ZFR than in ZLR, whereas basal values of mean arterial pressure (MAP) and heart rate (HR) were not significantly different. Increments of MAP (⌬MAP) and HR (⌬HR) elicited by electrical stimulation of the sciatic nerve (5-s trains of 100 pulses, 0.5-ms pulse duration, 100-to 400-A pulse intensity) were significantly higher (ANOVA, P Ͻ 0.05) in ZFR at each level of stimulus intensity. Regression analysis showed a linear increase in ⌬MAP and ⌬HR with increasing sciatic nerve stimulus intensity. Pressor responses to phenylephrine after ganglionic blockade demonstrated that vascular reactivity to adrenergic stimulation is not increased in ZFR compared with ZLR. Thus this factor does not contribute to enhancement of somatosympathetic reflexes observed in this strain. Insulin sensitivity in ZFR was onefourth (P Ͻ 0.05) that in ZLR. These results suggest that stronger sympathetic nervous reactivity in ZFR is associated with a severe insulin-resistant state before the onset of hypertension and support the hypothesis that insulin-mediated stimulation of the sympathetic nervous system is involved in the development of cardiovascular diseases related to alterations of glucose metabolism. sympathetic nervous activity; minimal model analysis; glucose kinetics; hypertension HYPERINSULINEMIA AND INSULIN resistance are considered important risk factors for development of hypertension (2, 39), and a number of studies have shown a significant association between hypertension and insulin resistance in obese and nonobese individuals (12,15,27,28,46). However, the pathophysiological relation among hyperinsulinemia, insulin resistance, and hypertension remains poorly understood.Some experimental reports suggest that an increase in sympathetic nervous system activity (SNA) may play a role in the association between insulin resistance and elevated blood pressure (39). This association might be due to a primary increase in sympathetic activity (22). Although an increase in sympathetic activity can cause hypertension and insulin resistance, studies performed on animal models indicate that the insulin resistance induced by a high-lipid diet occurs before the onset of hypertension (20), suggesting the primacy of the insulinmediated stimulation of the sympathetic nervous system. If this is true, a suitable animal model to investigate the mechanisms underlying insulin resistance and its associated pathologies is the obese Zucker rat, homozygous for the fa allele (fa/fa), in which a mutation of the leptin receptor-coding gene impairs the ability of leptin to suppress food intake. Homozygous ...

VO(dmpp)2 normalizes pre-diabetic parameters as assessed by in vivo magnetic resonance imaging and spectroscopy

“…In contrast, blood glucose concentration in non-treated obese rats remained high for at least 120 min (172.4 ± 1.3 mg/100 mL; P b 0.0005), and significantly different from all the other groups at this time point, as expected considering their typical glucose intolerant and insulin resistant profile [52].…”

Insulin resistance and impaired functional vasodilation in obese Zucker rats

“…However, we would suggest that these mild increases in BP exhibited in OZRs (29,41) and the short period of "hypertension" do not likely contribute to the severe impairment in AA metabolism and functional vasodilation. Indeed, a recent study (45) in OZRs showed that insulin resistancemediated stimulation of the sympathetic nervous system is related to altered glucose metabolism before the onset of hypertension.…”

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

“…At 7 wk of age, fasted OZR have elevated plasma levels of triglycerides and insulin (12,35,42). Although reports of differences in fasted levels of blood glucose between OZR and LZR at 7 wk are inconsistent, insulin resistance is unmistakable as evidenced by the hyperinsulinemia and impaired glucose tolerance (12,35,42). By adulthood, OZR have fasting hyperglycemia with elevated blood cholesterol and nonesterified fatty acids compared with juvenile OZR and age-matched LZR (12,37).…”