Effects of sodium salicylate on glucose kinetics and insulin signaling in postpartum dairy cows

Abstract

Low-grade inflammation has been implicated as a contributor to metabolic disease during the transition to lactation. In previous work, administration of sodium salicylate (SS) for 7 d led to hypoglycemia in mature dairy cows in early lactation. The purpose of this study was to identify the mode of action underlying this response to SS. Twenty mature (parity 3) cows were assigned alternately at time of calving to either control or SS treatments; the control received a molasses placebo in drinking water, whereas SS received 2.3 g/L of SS with the molasses carrier in drinking water for 7 d after parturition. Blood samples were collected daily. A glucose turnover assay was performed on d 7, followed by liver, muscle, and adipose tissue biopsies. There were no treatment effects on intake of dry matter or water. Tumor necrosis factor α mRNA abundance tended to be decreased by SS in adipose tissue but not in muscle or liver, and plasma haptoglobin and adiponectin concentrations were not altered by treatment. Treatment did not significantly alter plasma glucose or insulin concentrations, but plasma glucagon concentration tended to be increased by SS and the insulin: glucagon molar ratio was significantly decreased. Cows on SS had a tendency for a 25% decrease in glucose turnover rate compared with control cows. However, there were no differences in transcript abundance of pyruvate carboxylase (PC) or glucose-6-phosphatase (G6PC) in liver or of glucose transporter 4 (GLUT4) in any of the tissues. Finally, SS did not alter insulin receptor substrate-1 phosphorylation in muscle or adipose, but tended to increase phosphorylation of AMPactivated protein kinase and decrease protein kinase B phosphorylation in adipose tissue. These findings may be explained by enhanced hepatic insulin sensitivity leading to posttranscriptional suppression of gluconeogenesis and adaptive responses to decreased glucose supply in the pancreas and adipose tissue.

Review: Following the smoke signals: inflammatory signaling in metabolic homeostasis and homeorhesis in dairy cattle

“…We subsequently conducted a follow-up study where multiparous cows were treated with oral sodium salicylate, and plasma glucose turnover was determined with a stable isotope dilution method on day 7 of lactation. We found that glucose turner rate was decreased by 25%, despite a significant decrease in insulinglucagon ratio (Montgomery et al, 2019). Given the steadystate assumptions used in metabolic flux studies, the decline in glucose turnover reflected both a decreased use of glucose and a decreased supply.…”

Effect of anti-inflammatory treatment on systemic inflammation, immune function, and endometrial health in postpartum dairy cows

“…Other studies involving NSAID in the postpartum period appeared to improve liver function, with reductions in plasma AST and GLDH 29 . Moreover, oral anti-inflammatory medication in the first week postpartum resulted in greater hepatic insulin sensitivity 32,67,68 . Other early postpartum studies with NSAID have been performed, but the metabolic effects are not consistent 30 .…”

“…Similarly, cows treated with oral meloxicam produced more milk in early lactation, had reduced odds of subclinical mastitis, and reduced odds of early lactation culling 31 . In a recent study, Montgomery et al 32 explored the mechanistic role of inflammatory signaling in glucose and energy metabolism of dairy cows treated with sodium salicylate in drinking water in the first week postpartum. Although treated mature transition cows tended to suppress whole-body glucose turnover, no major differences were found in markers of SI and energy metabolism.…”

Transition Period of the Dairy Cow Revisited: I. Homeorhesis and Its Changes by Selection and Management

“…A growing body of evidence suggests that inflammation is involved in p.p. IR, and inflammation-dependent IR is thought to be an adaptive response of homeorhetic adaptation in early lactation (Farney et al, 2013;Montgomery et al, 2019).…”