Metabolic responses of lactating dairy cows to exogenous glucagon

Decreased concentrations of phospholipids, free cholesterol, and cholesteryl ester in plasma and liver are associated with fatty liver, a major metabolic disease of dairy cows in early lactation. The objective was to test whether daily subcutaneous injections of 7.5 and 15 mg of glucagon, which can decrease concentrations of liver triacylglycerol, affect concentrations of plasma lipoprotein components and liver lipids other than triacylglycerol. Multiparous Holstein cows (n = 32) were grouped on the basis of liver triacylglycerol concentrations at d 8 postpartum into "normal" (n = 8; triacylglycerol <1% liver wet wt) and "susceptible to fatty liver" (n = 24; triacylglycerol >1% liver wet wt) cows. Susceptible cows were assigned randomly to three groups and beginning at d 8 postpartum received 0 (same for Normal cows), 2.5, or 5 mg of glucagon by subcutaneous injections every 8 h for 14 d. In comparison to saline injections, subcutaneous injections of glucagon either increased or tended to increase concentrations of phospholipids and free cholesterol in liver, with greater increases of the latter during ambient temperatures below 35 degrees C. Glucagon injections decreased or tended to decrease concentrations of very low-density lipoprotein-triacylglycerol, high-density lipoprotein1-phospholipids, and high-density lipoprotein2-free cholesterol in plasma, with no changes of the latter two during ambient temperatures below 35 degrees C. The results indicate that subcutaneously administered glucagon has only minor effects on the lipid transport in plasma of dairy cows in early lactation with more beneficial effects occurring during ambient temperatures below 35 degrees C and, most importantly, no indications that glucagon has negative effects.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Exogenous Glucagon on Lipids in Lipoproteins and Liver of Lactating Dairy Cows

Bobe

Ametaj

Young

et al. 2003

“…Fatty liver (i. e., hepatic lipidosis) is one of the major metabolic disorders of dairy cows in the peripartal period, which affects up to 50% of cows in early lactation (Jorritsma et al, 2001). Fatty liver can negatively affect the productivity, health status, and reproductive performance of high-producing dairy cows (Herdt, 1988;Veenhuizen et al, 1991;Wensing et al, 1997;Bobe, 2002) and can be treated with continuous, intravenous infusions of glucagon for 14 d (Hippen et al, 1999b).…”

Section: Introductionmentioning

confidence: 99%

“…Administration of exogenous glucagon increases concentrations of plasma glucagon, glucose, and insulin in lactating dairy cows (de Boer et al, 1986;Trevisi et al, 1997;Hippen et al, 1999b;She et al, 1999) by stimulating hepatic gluconeogenesis, glycogenolysis, amino acid uptake, and ureagenesis (Flakoll et al, 1994;Donkin and Armentano, 1995). The metabolic response to glucagon depends on the dosage and the age, stage of lactation, and health of cows, with weaker responses at lower glucagon dosages in older, ketotic cows in early lactation (de Boer et al, 1986;Holtenius and Trå vén, 1990;Holtenius and Holtenius, 1996;Steen et al, 1997;Hippen et al, 1999aHippen et al, , 1999bShe et al, 1999;Bobe, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…The effects of glucagon on concentrations of plasma BHBA and NEFA can be both direct and indirect because glucagon directly increases lipolysis and ketogenesis (Brockman, 1976;Zupke et al, 1998) but indirectly decreases lipolysis and ketogenesis by increasing concentrations of plasma glucose and insulin (Brockman, 1978). Therefore, glucagon can either increase or decrease concentrations of plasma BHBA and NEFA depending on responses of glucose and insulin, dosage of glucagon, age, stage of lactation, and health of the cow, with increases being more likely at higher glucagon dosages in younger, ketotic cows in early lactation (de Boer et al, 1986;Hippen et al, 1999aHippen et al, , 1999bShe et al, 1999;Bobe, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Responses of Lactating Dairy Cows to Single and Multiple Subcutaneous Injections of Glucagon

Bobe

Sonon

Ametaj

et al. 2003

Continuous, intravenous infusions of glucagon improve carbohydrate status in lactating dairy cows without increasing concentrations of plasma NEFA. The objective was to test whether single subcutaneous injections and multiple subcutaneous injections of glucagon delivered at 8-h intervals over 14 d improve the carbohydrate status in lactating dairy cows without increasing concentrations of plasma BHBA and NEFA. In a single-injection experiment, four midlactation cows each were injected with 2.5 and 5 mg of glucagon 1 wk apart. In a multiple-injection experiment, nine cows, assigned randomly to three treatments, were injected subcutaneously with 0, 2.5, or 5 mg of glucagon every 8 h for 14 d, beginning at d 8 postpartum. Single subcutaneous injections of glucagon increased concentrations of plasma glucagon and single and multiple subcutaneous injections of glucagon increased concentrations of plasma glucose, with larger increases at the 5-mg dosage. Injections of 5 mg of glucagon increased concentrations of plasma insulin in both experiments, whereas the 2.5-mg dosage increased plasma insulin only in the multiple-injection experiment. The response of glucose and insulin to injections of 5 mg of glucagon persisted throughout the 14-d injection period. Concentrations of plasma NEFA decreased in the single-injection experiment, and concentrations of BHBA decreased after 5 mg of glucagon was injected in the multiple-injection experiment. These results document that both single and multiple injections of 5 mg of glucagon over 14 d consistently improve the carbohydrate status of dairy cows and decrease concentrations of plasma NEFA and BHBA.

Metabolic Changes and Net Portal Flux in Dairy Cows Fed a Ration Containing Rumen-Protected Fat as Compared to a Control Diet

Hammon

Metges

Junghans

et al. 2008

Feeding rumen-protected fat (RPF) is an alternative to increase energy density of the diet and therefore energy intake in dairy cows. To investigate metabolic and endocrine changes in dairy cows fed either a diet containing RPF (FD) or a control diet with an increased amount of cornstarch (SD), 3 Holstein cows (83 +/- 1 d in milk) were fitted with catheters in the portal vein, a mesenteric artery, and 2 mesenteric veins. Cows were fed consecutively SD and FD for 3 wk, respectively. In FD, cornstarch [92 g/kg of dry matter (DM)] was replaced by 50 g of RPF/kg of DM (mainly C16:0 and C18:1). Tracer infusions of NaH(13)CO3 and D-[U-(13)C6]glucose were performed into a jugular vein to measure rate of appearance and oxidation of glucose. Arterial and portal blood samples were collected to measure concentrations of glucose, lactate, volatile fatty acids, nonesterified fatty acids, beta-hydroxybutyrate, triglycerides, AA, insulin, and glucagon. Concomitantly, para-aminohippurate was infused into a mesenteric vein for measurement of portal plasma flow. Although DM intake was slightly lower in FD, protein and energy intakes were unaffected by diets. Milk and lactose yields were higher in FD than SD. Arterial plasma glucose concentration was lower with FD than SD, whereas nonesterified fatty acid and triglyceride concentrations were higher in FD. Glucagon concentration and glucagon-to-insulin ratio were both augmented by FD feeding. When feeding FD, greater milk and lactose yields, but not energy-corrected milk, were associated with elevated lipid status and higher glucagon concentrations but occurred despite lower plasma glucose concentration and were not linked with changes in whole body glucose rate of appearance. This study suggests a glucose-sparing effect allowing an enhanced lactose synthesis when feeding RPF.