Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A

Abstract

Early lactation in dairy cattle is a period of severe negative energy balance (NEB) characterized by reduced blood glucose and insulin concentrations and elevated blood GH concentrations. The liver is refractory to GH during NEB and this uncoupling of the GH-IGF axis results in diminished plasma concentrations of IGF-I. Our objectives were to examine the effects of insulin administration during the immediate postpartum period on plasma IGF-I and GH concentrations and to examine the hepatic expression of total GH receptors (all GH receptor transcripts), GH receptor 1A (GHR 1A) and IGF-I. In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue. Holstein cows (n=14) were subjected to either a hyperinsulinemic-euglycemic clamp (insulin; INS) or saline infusion (control; CTL) for 96 h starting on day 10 postpartum. Insulin was infused i.v. (1 µg/kg body weight per h), blood samples were collected hourly, and euglycemia was maintained by infusion of glucose. Insulin concentrations during the infusions were increased 8-fold in INS compared with CTL cows (2·33 0·14 vs 0·27 0·14 ng/ml (S.E.M.); P<0·001) while blood glucose concentrations were not different between treatments (45·3 2·2 vs 42·5 2·2 mg/dl; P>0·1). Plasma IGF-I increased continuously during the insulin infusion, and reached the highest concentrations at the end of the clamp, being almost 4-fold higher in INS compared with CTL cows (117 4 vs 30 4 ng/ml; P<0·001). Hepatic expression of GHR 1A and IGF-I mRNA was low in CTL cows, but was increased 3·6-fold (P<0·05) and 6·3-fold (P<0·001) respectively in INS cows. By contrast, in adipose tissue the changes in gene expression in response to insulin were reversed with decreases in both total GHR and IGF-I mRNA. The expressions of GHR 1A and IGF-I mRNA in liver tissue were correlated in INS (r=0·86; P<0·05), but not CTL cows (r=0·43; P>0·1). Insulin appears to be a key metabolic signal in coupling the GH-IGF axis, thus orchestrating a marked elevation in circulating IGF-I concentrations.

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

“…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. Therefore, it is possible that there is a minimum amount of insulin required to reduce the hepatic clearance of P 4 .…”

Effect of dietary energy source on energy balance, production, metabolic disorders and reproduction in lactating dairy cattle

“…Plasma NEFA and BHBA levels are recognized as indicators for body fat mobilization and NEB in dairy cattle in early lactation [22,48,55,57]. Decreased plasma glucose and insulin levels have been associated with NEB [12, 13, 57, 58] and increase as cows progress towards a more positive EB [59].…”

“…Secondly, research on the relation between glycogenic nutrient addition and EB and reproductive parameters is desirable since studies on this subject are still scarce. Some suggestions can be made since glucose and insulin are increased after feeding extra glycogenic nutrients and are suggested as positive metabolic signals to the reproductive axis [11,13,19,57,118,135]. Plasma NEFA and BHBA levels are increased after feeding extra lipogenic nutrients and associated with decreased reproductive performance and anestrous [9,65,[136][137][138].…”

Effect of exogenous insulin and fasting on growth hormone receptor and IGF-I expression in the pre-ovulatory follicle of ewes

“…However, the lack of correlation between GHR and IGF-I mRNA in the granulosa cells of large follicles has also been suggested in cattle (Rhoads et al, 2008), since there is no clear evidence that GH controls IGF-I secretion in the follicle (Lucy, 2000). Despite that, evidence indicates that IGFBP-2 to 26 (IGF-binding protein) are expressed in the ovine follicle (Hastie and Haresign, 2010) and that insulin levels can modulate free IGF-I availability through the modulation of IGFBP levels (Butler et al, 2003). In this way, although IGF-I mRNA expression was not different among groups, its intrafollicular availability could have been altered due to the effects of insulin on IGFBP.…”

“…This happens -E-mail: augusto.schneider@live.com because insulin concentration is reduced, and so is GHR expression in the liver (Butler et al, 2003). However, the infusion of insulin during negative energy balance is able to restore the coupling of the GH-IGF-I axis and increase circulating IGF-I concentration (Butler et al, 2003).…”