Glucose transport and milk secretion during manipulated plasma insulin and glucose concentrations and during LPS‐induced mastitis in dairy cows

Abstract

In dairy cows, glucose is essential as energy source and substrate for milk constituents. The objective of this study was to investigate effects of long-term manipulated glucose and insulin concentrations in combination with a LPS-induced mastitis on mRNA abundance of glucose transporters and factors involved in milk composition. Focusing on direct effects of insulin and glucose without influence of periparturient endocrine adaptations, 18 dairy cows (28 ± 6 weeks of lactation) were randomly assigned to one of three infusion treatments for 56 h (six animals each). Treatments included a hyperinsulinemic hypoglycaemic clamp (HypoG), a hyperinsulinemic euglycaemic clamp (EuG) and a control group (NaCl). After 48 h of infusions, an intramammary challenge with LPS from E. coli was performed and infusions continued for additional 8 h. Mammary gland biopsies were taken before, at 48 (before LPS challenge) and at 56 h (after LPS challenge) of infusion, and mRNA abundance of genes involved in mammary gland metabolism was measured by RT-qPCR. During the 48 h of infusions, mRNA abundance of glucose transporters GLUT1, 3, 4, 8, 12, SGLT1, 2) was not affected in HypoG, while they were downregulated in EuG. The mRNA abundance of alpha-lactalbumin, insulin-induced gene 1, κ-casein and acetyl-CoA carboxylase was downregulated in HypoG, but not affected in EuG. Contrary during the intramammary LPS challenge, most of the glucose transporters were downregulated in NaCl and HypoG, but not in EuG. The mRNA abundance of glucose transporters in the mammary gland seems not to be affected by a shortage of glucose, while enzymes and milk constituents directly depending on glucose as a substrate are immediately downregulated. During LPS-induced mastitis in combination with hypoglycaemia, mammary gland metabolism was more aligned to save glucose for the immune system compared to a situation without limited glucose availability during EuG.

Inflammatory and metabolic responses to an intramammary lipopolysaccharide challenge in early lactating cows supplemented with conjugated linoleic acid

“…The elevated basal insulin concentrations in the present study support earlier findings of Tsao et al. () and Lehnen, da Silva, Camacho, Marcadenti, and Lehnen (), who observed higher glycogen resynthesis in skeletal muscles by an increased glucose uptake via the insulin‐sensitive glucose transporter GLUT4 (Gross, van Dorland, Wellnitz, & Bruckmaier, ). Hints for positive impacts of CLA on the immune system were found in rats, chicken, mice (Cook, Miller, Park, & Pariza, ; Ntambi, Choi, Park, Peters, & Pariza, ) and humans (Albers et al., ).…”

“…Hötger et al (2013) assumed their findings on the reduced endogenous glucose production in CLAfed cows to reflect the reduced need for glucose, a more efficient use, and a potential glycogen resynthesis in muscle tissue. The elevated basal insulin concentrations in the present study support earlier findings of Tsao et al (2015) and Lehnen, da Silva, Camacho, Marcadenti, and Lehnen (2015), who observed higher glycogen resynthesis in skeletal muscles by an increased glucose uptake via the insulin-sensitive glucose transporter GLUT4 (Gross, van Dorland, Wellnitz, & Bruckmaier, 2015). Hints for positive impacts of CLA on the immune system were found in rats, chicken, mice (Cook, Miller, Park, & Pariza, 1993;Ntambi, Choi, Park, Peters, & Pariza, 2002) and…”

Invited review: Metabolic challenges and adaptation during different functional stages of the mammary gland in dairy cows: Perspectives for sustainable milk production

“…Infusing glucose in early lactation temporarily increased milk yield (Brown and Allen, 2013;Grossen-Rösti et al, 2018), although some authors argued that import capacities via GLUT and sodium-dependent glucose transporters into the mammary gland are limited (Zhao and Keat-ing, 2007b). In mid-to late-lactating cows, we could show that the expression of glucose transporters in the mammary gland seems to not be affected by a shortage of glucose forced by insulin infusion, whereas enzymes and milk components directly depending on glucose as precursor were immediately downregulated (Gross et al, 2015b). Conversely, during a hyperinsulinemic euglycemic condition in which glucose availability was not limited, glucose transporters were even downregulated (Gross et al, 2015b).…”

“…Most of the glucose is taken up into the mammary gland via insulin independent glucose transporter (GLUT) 1 (Zhao and Keating, 2007a,b). At later lactational stages, the importance of insulin-dependent glucose intake by, for example, GLUT4 increases (Mattmiller et al, 2011;Gross et al, 2015b), and the mammary gland is less dominant in draining glucose during an established nutrient homeostasis. The question of whether glucose in early lactation is limiting for milk synthesis was addressed by different approaches.…”

Glucose supplementation has minimal effects on blood neutrophil function and gene expression in vitro

“…During the inflammatory response, research has shown that systemic metabolic changes occur including increased circulating glucose concentrations in lactating dairy cows (Moyes et al, 2014) and nonlactating heifers (Steiger et al, 1999). Hence, glucose may be spared for utilization by phagocytic cells, such as PMNL, rather than the synthesis of milk components in the mammary gland as proposed by Gross et al (2014). During early lactation, glucose availability is low and may partly explain the natural immunosuppression observed at this time.…”