Short communication: Acute but transient increase in serum insulin reduces messenger RNA expression of hepatic enzymes associated with progesterone catabolism in dairy cows

Abstract

The objective of this experiment was to evaluate the effects of glucose infusion on serum concentrations of glucose, insulin, and progesterone (P4), as well as mRNA expression of hepatic CYP2C19 and CYP3A4 in nonlactating, ovariectomized cows in adequate nutritional status. Eight Gir × Holstein cows were maintained on a low-quality Brachiaria brizantha pasture with reduced forage availability, but they individually received, on average, 3 kg/cow daily (as fed) of a corn-based concentrate from d -28 to 0 of the experiment. All cows had an intravaginal P4-releasing device inserted on d -14, which remained in cows until the end of the experiment (d 1). On d 0, cows were randomly assigned to receive, in a crossover design containing 2 periods of 24h each (d 0 and 1), (1) an intravenous glucose infusion (GLUC; 0.5 g of glucose/kg of BW, over a 3-h period) or (2) an intravenous saline infusion (SAL; 0.9%, over a 3-h period). Cows were fasted for 12h before infusions, and they remained fasted during infusion and sample collections. Blood samples were collected at 0, 3, and 6h relative to the beginning of infusions. Liver biopsies were performed concurrently with blood collections at 0 and 3h. After the last blood collection of period 1, cows received concentrate and returned to pasture. Cows gained BW (16.5 ± 3.6 kg) and BCS (0.08 ± 0.06) from d -28 to 0. Cows receiving GLUC had greater serum glucose and insulin concentrations at 3h compared with SAL cohorts. No treatment effects were detected for serum P4 concentrations, although mRNA expression of CYP2C19 and CYP3A4 after the infusion period was reduced for cows in the GLUC treatment compared with their cohorts in the SAL treatment. In conclusion, hepatic CYP3A4 and CYP2C19 mRNA expression can be promptly modulated by glucose infusion followed by acute increases in circulating insulin, which provides novel insight into the physiological mechanisms associating nutrition and reproductive function in dairy cows.

Effects of supplementation of calcium salts of polyunsaturated fatty acids on serum concentrations of progesterone and insulin of pregnant dairy cows

“…Previous results from our laboratory have shown that peripheral concentrations of insulin potentially modulates the hepatic metabolism of P 4 (Moriel et al, 2008;Lopes et al, 2009;Vieira et al, 2010Vieira et al, , 2013. Elevated insulin concentrations reduced hepatic expression of P 4 catabolic enzymes P450 2C and P450 3A (Lemley et al, 2008;Vieira et al, 2013), which may further increase circulating concentrations of P 4 (Moriel et al, 2008;Lopes et al, 2009;Vieira et al, 2010).…”

“…Elevated insulin concentrations reduced hepatic expression of P 4 catabolic enzymes P450 2C and P450 3A (Lemley et al, 2008;Vieira et al, 2013), which may further increase circulating concentrations of P 4 (Moriel et al, 2008;Lopes et al, 2009;Vieira et al, 2010). Accordingly, Vieira et al (2013) reported that dairy cows in adequate nutritional status receiving jugular glucose infusion (3 h at a rate of 0.5 g/kg of BW) had greater circulating insulin concentrations and reduced hepatic mRNA expression of P 4 catabolic enzymes CYP2C19 and CYP3A4 compared with cohorts receiving saline infusion. Butler et al (2003) observed that hepatic clearance of P 4 is reduced linearly after increasing amounts of insulin infusion.…”

“…Williams and Stanko (2000) reported that cows supplemented with PUFA had greater circulating insulin concentrations when compared with nonsupplemented cohorts. The mechanisms by which insulin concentrations may affect P 4 concentrations include enhanced synthesis of P 4 through steroidogenesis (Butler et al, 2004), and reduced hepatic expression of P 4 catabolic enzymes P450 2C and 3A (Lemley et al, 2008;Vieira et al, 2013).…”

Effects of protein supplementation frequency on physiological responses associated with reproduction in beef cows1

“…Expression of CYP2C19 and CYP3A4 was assessed in samples collected at 0 and 4 h relative to supplementation on d 18, from cows that responded to the estrus synchronization protocol, based on previous research from our group (Vieira et al, 2013).…”

Produção embrionária, perfil endócrino, metabólico e molecular de vacas holandesas não-lactantes recebendo dieta à base de milho ou polpa cítrica

“…No presente estudo, no entanto, esse efeito "protetor" não foi relacionado à menor expressão gênica das enzimas que metabolizam a P4 (CYP2C19, CYP3A4, AKR1D1, AKR1C4), visto que não foi encontrada diferença na expressão gênica (Tabela 10), diferente do descrito por Lemley et al (2008). Outros autores também não encontram diferença na expressão gênica dessas enzimas após estímulo com insulina MATTOS, 2012) enquanto que no estudo de Vieira et al (2013) o desafio com insulina diminuiu a expressão das enzimas CYP2C19 e CYP3A4, mas não alterou a P4 circulante.…”