Masters Theses

Date of Award

8-1983

Degree Type

Thesis

Degree Name

Master of Science

Major

Animal Science

Major Professor

Richard N. Heitmann

Committee Members

H. G. Kattesh, J. T. Smith

Abstract

Eleven ewes weighing between 55 and 65 kg were randomly placed in one of three experimental categories: normal (n=5); diabetic insulin-treated, DIT (.n=3); and diabetic 72-hour-untreated, DUT (.n=3). Animals were rendered diabetic pharmacologically via intravenous doses of alloxan (50 mg/kg). The femoral artery and vein, along with the portal, hepatic, and mesenteric veins were cannulated immediately prior to each experiment. Experiments were therefore conducted in anesthetized (sodium pentobarbital) animals following surgery. Mesenteric infusion of para-aminohippuric acid (PAH) was used to determine whole blood flow rates across the splanchnic tissues. Three sets of preinfusion or control samples were obtained at 15-minute intervals immediately followed by continuous infusion of β-hydroxybutyrate into the caudal vena cava with four subsequent serial whole blood samples obtained from the femoral artery, and portal and hepatic veins at 30-minute intervals. The whole blood samples were analyzed for β-hydroxybutyrate, acetoacetate, and PAH, and plasma analyzed for free fatty acids and insulin. As expected, free fatty acid levels were depressed by β-hydroxy-butyrate infusion in the normal, DIT, and DUT animals. Since there was a concomitant decrease in net hepatic and total splanchnic uptake of free fatty acids, the concentration changes must have been due to decreased peripheral tissue lipolysis. Infusion of β-hydroxybutyrate increased pancreatic insulin release, but there was a corresponding hepatic uptake of the hormone, and thus, no net change in total splanchnic insulin flux was observed. In the normal and DIT, but not the DUT sheep, a net increase in total splanchnic acetoacetate uptake and a concomitant decrease in net total splanchnic β-hydroxybutyrate release during infusion of the ketone body was observed. From these results it was concluded that the effects of β-hydroxybutyrate infusion on ketone body and free fatty acid concentrations and fluxes may be mediated at the insulin receptor site and not by increased pancreatic insulin production.

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