The Hyperinsulinemia Produced By Concanavalin A In Rats Is Opioid- Dependent And Hormonally Regulated

The present study examines the effect of concanavalin A (Con A) on the blood insulin and glucose levels of rats. Male and female rats treated with Con A (62.5-500 μg/kg) for three days sowed a dose- and time-dependent hyperinsulinemia that listed more than 48 h. Male rats were more sensitive to Con A. Thus, 6 h after treatment with Con A the circulating insulin levels in male rats had increased by 85% (control: 10.2 ± 0.9 mU/l and Con A-treated: 10.3 ± mU/l) in females. An identical response was seen after 12 h. Con A (250 μg/kg) produced time-dependent hypoglycemia in both sexes but more pronounced in males. There was no correlation between the hypoglycemia and hyperinsulinemia described above. The Con A-induced hyperinsulinemia in rats of both sexes was abolished in gonadectomized animals, P<0.05) while testosterone (10 mg/kg, im) had no similar effect on intact female rats. Pretreating Con A-injected rats with opioid antagonists such as naloxone (1 mg/kg, sc) and naltrexone (5 mg/kg, sc) blocked the hyperinsulinemia produced by the lectin in males (control: +101 ± 17% vs naloxone-treated: +5 ± 14%, or naltrexone-treated: -23 ± 4.5%) and females (control: +86 ± 23% vs naloxone-treated: +21 ± 20%, or naltrexone-treated: -18 ± 11%). These results demonstrates that Con A increases the levels of circulating insulin in rats and that this response is opioid-dependent and hormonally regulated.31569770

Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice

Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2- macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Numbers R56DE020097 (SW) and F32DE026366 (JR

The hind paw edema produced by stahylococcal enterotoxin B in female mice is modulated by sex hormones

This paper describes the involvement of sex hormones in the edematogenic response produced by staphylococcal enterotoxin B (SEB) in the mouse hindpaw. Both the paw weight variation and the protein exudate produced by the intraplantar administration of SEE (12.5 mu g/paw) to intact, randomly cycling female (IRCF) mice were significantly attenuated when the animals were ovariectomized (OVX). The attenuation of SEB-induced paw swelling produced by OVX was not reversed by estradiol (OE2) reposition. Thus, 4 h after the injection of SEE the increase in paw weight in OVX-mice treated with OE2 (10 mu g/kg in corn oil) was 15.0 +/- 0.9 mg, while the exudation corresponded to 2.1 +/- 0.3 mu g of Evans blue dye/g of tissue. Neither of these values differed significantly from those obtained 4 h after the intraplantar injection of SEE (12.5 mu g/paw) in non-treated OVX-mice (paw swelling, 14.0 +/- 0.8 mg; dye exudation, 2.0 +/- 0.3 mu g/g, N = 6). Pretreating IRCF mice once a day for three days with human chorionic gonadotrophin (40 IU/kg, i.m.) reduced the paw edema produced by the toxin, thus indicating an involvement of gonadotrophins in this event. A pronounced decrease in paw weight variation (about 45%) and dye exudation (61%) was detected when IRCF mice were previously treated every 72 h with three injections of OE2 (10 mu g/kg in corn oil, i.m.). Similar situations were also seen when the animals were pretreated at 72 h intervals with three injections of testosterone (10 mg/kg in corn oil, i.m.). We conclude that the paw edema induced by SEE in female mice is hormonally regulated. Our results also indicate that the HPA-immune axis is involved in this phenomenon.8217918

Neutrophil migration induced by staphylococcal enterotoxin type A in mice: a pharmacological analysis

Staphylococcal enterotoxin type A induced marked neutrophil migration into the mouse peritoneal cavity and was dependent on the number of resident macrophages. This migratory response was dose- (16-64 mu g of staphylococcal enterotoxin type A/cavity) and time-dependent, peaking at 12 h and disappearing after 72 h. Dexamethasone (0.5 mg/kg) inhibited the neutrophil migration induced by staphylococcal enterotoxin type A (32 mu g; 42% inhibition). A similar response was observed with the platelet-activating factor-acether receptor antagonist, BN 52021 (ginkgolide B, 3-(1,1-dimethylethyl)-hexahydro-1,4-7b-trihydroxy-8-methyl-9H-1,7 alpha (epoxymethanol 1H,6 alpha H-cyclopenta (c) furo (2,3-b) furo (3', 2': 3,4) cyclopenta (1,2-d) furan-5, 9, 12 (4H)-trione); 10 mg/kg; 57% inhibition), the histamine H-2 receptor antagonist, cimetidine (2 mg/kg; 31% inhibition), the lipoxygenase inhibitor, BWA4C (N-(3-phenoxycinnamyl) acetohydroxamic acid); 10 mg/kg; 73% inhibition), and capsaicin (trans-8-methyl-N-vanilyl-6-nonamide), a sensory C-fiber neuropeptide depletor. In contrast, indomethacin (5 mg/kg) had no effect on staphylococcal enterotoxin type A-induced chemotaxis. We conclude that the peritonitis induced by staphylococcal enterotoxin type A in mice is macrophage-dependent. The mechanism whereby staphylococcal enterotoxin type A stimulates macrophages to induce neutrophil recruitment remains to be elucidated. (C) 1998 Elsevier Science B.V. All rights reserved.3634170018919

Increased Insulin Circulating Levels Induced By Canatoxin In Rats.

Canatoxin, a proteic neurotoxin from Canavalia ensiformis seeds, raises circulating insulin levels and induces hypoglycemia in rats. The hyperinsulinemia produced by canatoxin (6 micrograms kg-1, 20 min; 108% of increase in female rats) was both time and dose dependent and lasted only about 30 min, while the fall in blood glucose levels (around 30%) was long lasting. The hyperinsulinemic response to canatoxin was greater in females (+108 +/- 18%) than males (+43 +/- 8%), but no difference was noted in the hypoglycemia. Pretreatment of rats with either naloxone, naltrexone, atropine or hexamethonium abolished both the hyperinsulinemia and the hypoglycemia. These data suggest that these phenomena are influenced by opioids and depend on parasympathetic stimulation.311131-

Sex-related Canatoxin-induced Blood Glucose Alterations In The Rat

[No abstract available]221215071513MEXT; Science and Technology Facilities Council; STFC; Science and Technology Facilities Counci

Intracerebroventricular Administration Of Canatoxin To Rats Increases The Circulating Levels Of Luteinizing Hormone.

Recent evidence has implicated the central nervous system as a target organ for canatoxin, a toxic protein present in Canavalia ensiformis seeds. This toxin activates the lipoxygenase pathway of arachidonic acid metabolism and can thus induce the release of substances mediated by lipoxygenase products. In the present study, the circulating levels of luteinizing hormone (LH) were measured by RIA in male Wistar rats (200-240 g) after the administration of canatoxin into the lateral cerebral ventricle. Canatoxin (0.5-2 micrograms in 2 microliters daily for 3 days) caused a dose- and time-dependent increase in the plasma levels of LH. The total dose of canatoxin used is subconvulsive. At 2, 4 and 24 h after 2 micrograms of canatoxin LH levels were increased by 10%, 43% and 61%, respectively, compared to vehicle-injected animals (0.18 +/- 0.03 ng/ml). This response to 2 micrograms of canatoxin was not attenuated by pretreatment with two different lipoxygenase inhibitors, nordihydroguaiaretic acid (NDGA, 125 mg/kg) or esculetin (ECLT, 125 mg/kg), ip, 1 h before each canatoxin (CNTX) injection; % increase in LH with CNTX alone: 61%; CNTX+NDGA: 54%; CNTX+ECLT:76%; N = 5/group. These data show that intracerebral injection of CNTX in rats increases circulating levels of LH via a mechanism that is independent of the lipoxygenase pathway.26111231123