The hyperinsulinemia produced by concanavalin A in rats is opioid-dependent and hormonally regulated

Abstract

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 showed a dose-and time-dependent hyperinsulinemia that lasted 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: 18.8 ± 1 mU/l) compared to only 38% (control: 7.5 ± 0.2 mU/l; 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 (intact males: +101 ± 17% vs orchiectomized males: -5 ± 3%; intact females: +86 ± 23% vs ovariectomized females: -18 ± 7.2%). Pretreating intact male and female rats with human chorionic gonadotropin also significantly inhibited the Con A-induced hyperinsulinemia. Estradiol (10 µg/kg, im) significantly blocked the Con A-induced increase in circulating insulin in male rats (101 ± 17% for controls vs 32 ± 5.3% for estradiol-treated 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 naloxonetreated: +5 ± 14%, or naltrexone-treated: -23 ± 4.5%) and females (control: +86 ± 23% vs naloxone-treated: +21 ± 20%, or naltrexonetreated: -18 ± 11%). These results demonstrate that Con A increases the levels of circulating insulin in rats and that this response is opioiddependent and hormonally regulated.

The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4

“…Further, Sukumar, Viswambharan (49) identified a NOX enzyme as a contributor in insulin resistance-mediated oxidative stress and postulated that its pharmacological inhibition may possess a novel therapeutic target in insulin resistance-related diseases. In this context, rats injected with ConA showed a significant serum hyperinsulinemia in accordance with FranciscoDoPrado, Zambelli (50). Pretreatment with either apocynin or α-LA significantly counteracted the effect of ConA on serum insulin.…”

Systematic review of sex-based differences in opioid-based effects

“…One study reported limited evidence of sex-based differences in basal transmission and long-term potentiation (LTP) outcomes within male and female rat hippocampal slices following administration of the fast-acting opioid antagonist naloxone (Harte-Hargrove, Varga-Wesson, Duffy, Milner, & Scharfman, 2015), but did note that naloxone enhanced mossy fiber transmission in females during proestrus but not males. A study on hyperinsulinemia (excess insulin relative to glucose) reported that pretreating concanavalin A-injected rats with the opioid antagonists naloxone or naltrexone blocked the hyperinsulinemia produced by lectin in males and females, suggesting that concanacalin A may increase the levels of circulating insulin in rats in a manner that is opioid-dependent and hormonally-regulated (Francisco-DoPrado, Zambelli, Melo-Lima, & Ribeiro-DaSilva, 1998).…”

Opioid‐like antinociceptive effects of oral administration of a lectin purified from the seeds of Canavalia brasiliensis

“…The involvement of the opioid system in lectin activity has already been demonstrated, as in the naloxone‐induced reversion of the antinociceptive effect of lectins from Bryothamnion seaforthii , Bryothamnion triquetrum , and C. boliviana [4,7] and the opioid regulation of hyperinsulinemia by the lectin from Canavalia ensiformis (which is 99% homologous with ConBr) [41].…”