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

Bobe, Gerd; Sonon, R.N.; Ametaj, Burim N.; Young, J.W.; Beitz, Donald C.

doi:10.3168/jds.s0022-0302(03)73796-5

Cited by 20 publications

(52 citation statements)

References 24 publications

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“…Chronic administration of exogenous glucagon in animals generated hypolipemidemic effects, with reduced plasma TG, FFA, and cholesterol; decreased VLDL secretion from the liver; increased hepatic fatty acid (FA) oxidation; and decreased hepatic accumulation of lipid (21,36–38). Glucagon decreased plasma FFAs and VLDL-TG and prevented fatty liver in dairy cows receiving daily injections of glucagon for 2 weeks (21,39,40). In rats receiving daily injections of glucagon for 8 or 21 days, TG in chylomicron and VLDL (22,37,41) and plasma cholesterol concentrations were decreased (36,37).…”

Section: Discussionmentioning

confidence: 99%

“…It is important to be cognizant of the fact that in chronic studies potential confounding effects due to compensatory secretion of other hormones, such as insulin, and changes in plasma FFA and glucose concentrations, cannot be ruled out. Indeed, concomitant increase of insulin was detectable in dairy cows after glucagon injection, at least transiently (39). …”

Section: Discussionmentioning

confidence: 99%

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Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

et al. 2011

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OBJECTIVEThe metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans.RESEARCH DESIGN AND METHODSEight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL).RESULTSThere were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P < 0.05) VLDL1 apoB100 fractional catabolic rate (−39%) and production rate (−30%) in HG versus BG, but no difference in de novo lipogenesis or TG turnover, and glucagon had no effect on intestinal (B48-containing) lipoprotein metabolism.CONCLUSIONSGlucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

et al. 2011

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“…69 Improved glucose status with decreased nonesterified fatty acids and β-hydoxybutyrate was also reported. 70 …”

Section: Beyond Glucose Homeostasismentioning

confidence: 99%

“…Studies in cattle suggest that glucagon may be an effective treatment for fatty liver and dyslipidemia 124 without deleterious effects on glucose homestasis, as both single and multiple injections of 5 mg glucagon over 14 days consistently improve the carbohydrate status of dairy cows and decreased concentrations of plasma nonesterified fatty acids. 70 Of course, these actions must be verified in nonruminant species.…”

Section: Beyond Glucose Homeostasismentioning

confidence: 99%

The metabolic actions of glucagon revisited

et al. 2010

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The initial identification of glucagon as a counter-regulatory hormone to insulin revealed this hormone to be of largely singular physiological and pharmacological purpose. Glucagon agonism, however, has also been shown to exert effects on lipid metabolism, energy balance, body adipose tissue mass and food intake. The ability of glucagon to stimulate energy expenditure, along with its hypolipidemic and satiating effects, in particular, make this hormone an attractive pharmaceutical agent for the treatment of dyslipidemia and obesity. Studies that describe novel preclinical applications of glucagon, alone and in concert with glucagon-like peptide 1 agonism, have revealed potential benefits of glucagon agonism in the treatment of the metabolic syndrome. Collectively, these observations challenge us to thoroughly investigate the physiology and therapeutic potential of insulin's long-known opponent.

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“…The Kronecker product of a completely unrestricted variance-covariance matrix (for LPS dose) and a first-order autoregressive variance-covariance matrix (for time after LPS administration) was used to account for double repeated measures taken on individual cows across time. 19 Multiple differences between treatments were tested by the SLICE option. Data of peripartal responses were analyzed according to the model described previously.…”

Section: Statistical Analysesmentioning

confidence: 99%

Oral challenge with increasing doses of LPS modulated the patterns of plasma metabolites and minerals in periparturient dairy cows

et al. 2012

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We showed recently that repeated oral exposure to LPS stimulated humoral immune responses in periparturient dairy cows. Here, metabolic and mineral responses to repeated oral administration of LPS were investigated. Sixteen clinically healthy, pregnant Holstein cows were orally administered 3 ml of saline solution (control) or 3 ml of saline solution containing 3 increasing doses of LPS, at 07:00 h, as follows: (i) 0.01 µg/kg body mass (BM) on d -14 and -10, (ii) 0.05 µg/kg BM on d -7 and -3, and (iii) 0.1 µg/kg BM on d 3 and 7 relative to parturition. Blood samples were measured shortly before, and at 8 different time-points after (up to 6 h), the first challenge of each LPS dosage to evaluate the post-challenge plasma profile, as well as weekly up to 4 wk postpartum. Results showed that oral administration of LPS lowered concentrations of non-esterified fatty acids (P < 0.01) and β-hydroxy-butyrate (P < 0.01) in the plasma, particularly after the third LPS challenge. Also, after the third oral LPS challenge, treatment tended to increase plasma glucose. Plasma calcium did not change, but concentrations of insulin (P < 0.01) and zinc (P < 0.01) were greater, while that of copper was lower (P < 0.01) in the plasma of treated cows. This is the first report to indicate a potential role for repeated oral administration of LPS around parturition to modulate the profile of plasma metabolites and minerals postpartum.

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

Cited by 20 publications

References 24 publications

Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

The metabolic actions of glucagon revisited

Oral challenge with increasing doses of LPS modulated the patterns of plasma metabolites and minerals in periparturient dairy cows

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