Autoregulation of ketogenesis in fasted sheep

Abstract

The effects of beta-hydroxybutyrate at rates simulating maximum utilization on portal-drained viscera (PDV), hepatic (HEP), and hindquarter (rump) net fluxes of acetoacetate (AcAc), beta-hydroxybutyrate (BOHB), free fatty acids (FFA), insulin (IN) and glucagon (GN) were measured in normal (NOR), diabetic insulin treated (DIT) and diabetic untreated (OUT) 3-day fasted sheep. The sheep were equipped with chronic indwelling catheters in the femoral artery and portal, hepatic, mesenteric, and femoral veins. Beta-hydroxybutyrate was infused into a jugular vein. Para-aminohippuric acid (PAH) was infused into a mesenteric vein (1.5% at 0.764 ml/min) in order to measure blood flow rates across the downstream tissues. Hindquarter blood flow was determined by infusing PAH into the femoral artery and measuring femoral artery-jugular vein PAH differences. Three pre- and post-BOHB samples were taken simultaneously from the artery and portal, hepatic, and femoral veins. Net fluxes were calculated by multiplying venoarterial differences by whole blood flow rates. Briefly, BOHB infusion decreased FFA levels in the NOR and DIT and to a lesser extent in CUT animals. Hepatic uptake of FFA decreased in NOR and DIT, but not DOT. Portal-drained visceral and RUMP release of FFA decreased in NOR and DIT, but not DUT ewes. Production of both AcAc and BOHB decreased during BOHB infusion in all three groups. Betahydroxybutyrate infusion increased pancreatic production of insulin in the DIT and NOR sheep but had no effect on IN levels in DUT sheep, while exerting no effect on GN production

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