Impaired sympathoadrenal axis function contributes to enhanced insulin secretion in prediabetic obese rats

Abstract

The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.

Figure 1

Sympathetic activity in MSG-obese rats. The bars represent the frequency of nerve discharges in mean ± SEM (n = 8 animals per group). Student's t-test was used. *P < 0.05 compared to control, by Student's t-test. Representative records of nerve discharges from a control and MSG-obese animal are shown.

Figure 2

Adrenal medulla total catecholamine content, basal catecholamine secretion, and blood circulating adrenaline concentration in MSG-obese rats. The bars represent mean ± SEM (n = 10–15 animals per group). *P < 0.05 compared to control, by Student's t-test.

Figure 3

Adrenal catecholamine secretion in MSG-obese rats. The bars represent mean ± SEM (n = 8–10 animals per group). *P < 0.05 compared to control, by Student's t-test.

Figure 4

TH and α-PKC expression in MSG-obese rats. The (a,b) bars represent mean ± SEM (n = 6–9 animals per group). *P < 0.05 compared to control, by Student's t-test. Representative Western blots of TH and PKC are shown in the middle and lower panels, respectively.

Figure 5

Glucose-stimulated insulin secretion and the inhibitory action of adrenaline on insulin secretion in MSG-obese rats. For each glucose concentration, 20 measurements, from islets isolated from 5 animals were performed. The data are shown as mean ± SEM. *P < 0.05 compared to control, by Student's t-test.

Figure 6

The effect of the α-adrenergic agonist oxymetazoline on glycaemia (a) and insulinaemia (b) during ivGTT in MSG-obese rats. Bars represent mean ± SEM (n = 8–10 animals per group). A Student's t-test or ANOVA was used where appropriate. *P < 0.05 compared to control. The letters over the bars represent a significant difference: a: P < 0.05 versus control; b: P < 0.05 versus control-oxymetazoline; c: P < 0.05 versus MSG; d: P < 0.05 versus MSG xymetazoline.