Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis.
The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like it is shown in humans, but was able to impact hyperlipemia, as NEFA and TG decreased.
Institute of Animal Nutrition, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Braunschweig, Germany.
Kirsten
K
Schulz
Institute of Animal Nutrition, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Braunschweig, Germany.
Jana
J
Frahm
Institute of Animal Nutrition, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Braunschweig, Germany.
Susanne
S
Kersten
Institute of Animal Nutrition, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Braunschweig, Germany.
Ulrich
U
Meyer
Clinic for Cattle, University of Veterinary Medicine Hannover, Hannover, Germany.
Jürgen
J
Rehage
Clinic for Cattle, University of Veterinary Medicine Hannover, Hannover, Germany.
Marion
M
Piechotta
Clinic for Cattle, University of Veterinary Medicine Hannover, Hannover, Germany.
Maria
M
Meyerholz
Department of Physiology, University of Veterinary Medicine Hannover, Hannover, Germany.
Gerhard
G
Breves
Boehringer Ingelheim Vetmedica, Ingelheim am Rhein, Germany.
Dania
D
Reiche
Physiology and Hygiene Unit, Institute of Animal Science, University of Bonn, Bonn, Germany.
Helga
H
Sauerwein
Institute of Animal Nutrition, Federal Research Institute for Animal Health, Friedrich-Loeffler-Institute, Braunschweig, Germany.
Sven
S
Dänicke
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D007662:Ketosis / Q000188:drug therapy / Q000662:veterinary*; D008099:Liver / Q000201:enzymology
D054873:Dipeptidyl-Peptidase IV Inhibitors; D018819:Dipeptidyl Peptidase 4