WOOD AJJ, WOOD M. The effect of advancing age on the sympathetic response to laryngoscopy and tracheal intubation. Anesth Analg 1989;68:603-8.

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Previous studies using male rodents showed the adipocyte-derived hormone leptin acts in the brain to regulate cardiovascular function, energy balance and glucose homeostasis. The importance of sex differences in cardiometabolic responses to leptin, however, is still unclear. We examined potential sex differences in leptin's chronic central nervous system (CNS)-mediated actions on blood pressure (BP), heart rate (HR), appetite, and glucose homeostasis in normal and type 1 diabetic rats. Female (n=6) and male (n=5) Sprague-Dawley rats were instrumented with intracerebroventricular (ICV) cannulas for continuous 7-day leptin infusion (15 mg/day) and BP and HR were measured by telemetry 24-hrs/day. At baseline, females had lower MAP (96±3 vs. 104±4 mmHg, p<0.05) but higher HR (375±5 vs. 335±5 bpm, p<0.05) compared to males. Following leptin treatment, we observed similar changes in BP (~3 mmHg) and HR (~25 bpm) in both sexes. Females had significantly reduced body weight (BW, 283±2 vs. 417±7 g, p<0.05) and lower caloric intake (162±20 vs. 192±9 kcal/kg of BW, p<0.05) compared to males, and leptin infusion reduced BW (-10%) and caloric intake (-62%) similarly in both sexes. Leptin infusion also caused similar reductions in fasting insulin and blood glucose levels in both sexes. In female and male rats with streptozotocin-induced diabetes (n=5/sex), ICV leptin treatment for 7 days completely normalized glucose levels. These results show that leptin's CNS effects on BP, HR, glucose regulation and energy homeostasis are similar in male and female rats. Therefore, our results provide no evidence for sex differences in leptin's brain-mediated cardiovascular or metabolic actions.

Current clinical antidiabetic drugs, like rosiglitazone 1, have been implicated in some serious side effects like edema, weight gain, and heart failure, making it necessary to find alternative agents. Partial agonists of peroxisome-proliferator activated receptor-gamma (PPARγ) were determined to possess improved insulin sensitivity without undeseirable side-effects when compared to full agonists of PPARγ, like rosiglitazone 1. The traditional Chinese medicine (TCM) plants, Goji (Lycium barbarum and Lycium chinense) are widely used for treating symptoms related to various diseases including diabetes and hypertension. Twenty-seven reported compounds from Goji were docked into both partial-and full-agonist binding sites of PPARγ. Amongst the docked compounds, phenylethylamide-based phytochemicals (5-9) (termed as tyramine-derivatives, TDs) were found to possess good docking scores and binding poses with favorable interactions. Synthesis of 24 TDs, including three naturally occuring amides (6, 8, 9) were synthesized and tested for PPARγ gene induction with cell-based assay. Three compounds showed similar or higher fold induction than the positive control, rosiglitazone. Among these three active TDs, trans-N-feruloyloctopamine (9) and tyramine derivatives-enriched extract (TEE) (21%) of the root bark of L. chinense were further studied in vivo using db/db mice. However, both TEE as well as 9 did not show significant antidiabetic properties in db/db mice. In vivo results suggest that the proposed antidiabetic property of Lycium species may not be due to tyramine derivatives alone. Further studies of tyramine derivatives or enriched extract(s) for other bioactivities like hypocholesterolemic activities, and studies of novel isolated compounds from Goji will enable a more complete understanding of their bioactivities.

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