Increase in visceral fat per se does not induce insulin resistance in the canine model.

OBJECTIVES: To determine whether a selective increase of visceral adipose tissue content will result in insulin resistance. METHODS: Sympathetic denervation of the omental fat was performed under general inhalant anesthesia by injecting 6-hydroxydopamine in the omental fat of lean mongrel dogs (n = 11). In the conscious animal, whole-body insulin sensitivity was assessed by the minimal model (SI ) and the euglycemic hyperinsulinemic clamp (SICLAMP ). Changes in abdominal fat were monitored by magnetic resonance. All assessments were determined before (Wk0) and 2 weeks (Wk2) after denervation. Data are medians (upper and lower interquartile). RESULTS: Denervation of omental fat resulted in increased percentage (and content) of visceral fat [Wk0: 10.2% (8.5-11.4); Wk2: 12.4% (10.4-13.6); P < 0.01]. Abdominal subcutaneous fat remained unchanged. However, no changes were found in SI [Wk0: 4.7 (mU/l)(-1) min(-1) (3.1-8.8); Wk2: 5.3 (mU/l)(-1) min(-1) (4.5-7.2); P = 0.59] or SICLAMP [Wk0: 42.0 × 10(-4) dl kg(-1) min(-1) (mU/l)(-1) (41.0-51.0); Wk2: 40.0 × 10(-4) dl kg(-1) min(-1) (mU/l) (-1) (34.0-52.0); P = 0.67]. CONCLUSIONS: Despite a selective increase in visceral adiposity in dogs, insulin sensitivity in vivo did not change, which argues against the concept that accumulation of visceral adipose tissue contributes to insulin resistance.

The sympathetic nervous system is involved in the inhibitory effect of morphine on the colon motility in rats.

The role of the sympathetic nervous system in the inhibitory effect of morphine on colonic motility was investigated in male adult Wistar rats. The responses of colonic motility and blood pressure to the intravenous administration of morphine under urethane anesthesia were recorded. Sympathectomy (6-hydroxydopamine) or pretreatment with phentolamine, an alpha-adrenoreceptor antagonist (3.15 microM/kg, i.v.), or propranolol, a beta-adrenoreceptor antagonist (3.38 microM/kg, i.v.), on the inhibitory effect of intravenously administered morphine on colonic motility were observed. The results of the investigation showed that a significant depression of colonic motility occurred in untreated rats following intravenous administration of morphine, while no significant effect was seen in the sympathectomized. Pretreatment with phentolamine or propranolol also significantly attenuated the depression of colonic motility induced by morphine. Morphine also produced a transient depression of the blood pressure. However, this inhibitory effect of morphine on blood pressure was intensified after sympathectomy or pretreatment with either phentolamine or propranolol. We conclude that sympathetic activity plays an important role in the inhibitory effects of morphine on colonic motility and that both alpha- and beta-adrenoreceptors are involved.

The effect of central sympathectomy by 6-hydroxydopamine (6-OHDA) on the response to morphine in conscious sheep.

When morphine, an opioid mu-agonist, was administered in vivo into the third cerebral ventricle (ICV) of conscious sheep at 20 and 40 micrograms/kg body weight, it caused psychomotor excitability for 2-3 h and a significant decrease in the reticuloruminal frequency for 45 min and in the mean amplitude of the primary contractions for 65 min. From 60 min after infusion, the same doses of morphine caused a significant increase in the average amplitude of the contractions for 45 min. This suggests that an inhibitory mu-opioid acceptor is involved in the central control of forestomach motility and general behaviour in sheep. All the effects of morphine were completely prevented by pretreatment with 18.2 micrograms/kg body weight 6-OHDA ICV. These results suggest that both morphine-induced inhibition of rumen motility and psychomotor excitability are due to central noradrenergic descending system activation. The exact location of the noradrenergic system remains to be determined.