Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep.

Epinephrine caused hyperglycemia in part by increasing gluconeogenesis. However, the mechanism of its gluconeogenic effects has not been studied in ruminants. This study was undertaken to examine the effect of epinephrine on the net hepatic uptake of selected glucose precursors in sheep. The major abdominal blood vessels of the sheep were catheterized in normal and alloxan diabetic sheep. Glucose production, metabolic clearance of glucose, and the hepatic removal of certain glucose precursors were determined before, during, and after epinephrine infusion. Epinephrine increased the hepatic glucose output, the concentrations of lactate and glycerol in plasma, and the net hepatic uptake and fractional hepatic extraction of lactate and glycerol. These effects were independent of changes in the concentrations of insulin and glucagon in plasma. These results show that epinephrine directly stimulates hepatic gluconeogenesis in sheep.

Effect of insulin on the utilization of propionate in gluconeogenesis in sheep.

The effects of insulin on the utilization of propionate in glucose synthesis were studied in fed and fasted sheep. Insulin was infused at 0.40 microU/h into the mesenteric vein. Glucose was infused to prevent hypoglycaemia. The rate of incorporation of [2-14C]propionate into glucose was determined before and during insulin infusion. After 150 min of insulin infusion endogenous glucose synthesis was about 70% of control values, whereas the incorporation of [14C]propionate into plasma glucose was 94% of control values. In contrast, the incorporation of other glucose precursors into glucose was decreased 30-50% by insulin. Therefore, insulin does not appear to decrease the utilization of propionate in gluconeogenesis. These results are consistent with the proposition that insulin differentially affects the rate of incorporation of glucose precursors into glucose in ruminant animals.

Effect of exercise on net hepatic uptake of lactate, pyruvate, alanine, and glycerol in sheep.

Gluconeogenesis increases during exercise, which is associated with elevated concentrations of lactate and glycerol in blood. This study was undertaken to determine if the exercise-induced increase in gluconeogenesis is due to increased hepatic extraction efficiency of glucose precursors. The net hepatic uptake and extraction ratios were determined for selected glucose precursors before and during exercise. The hepatic uptake of lactate and glycerol increased during exercise in fed and fasted animals, but extraction ratios of lactate and glycerol increased only in fed animals. Thus, the exercise-induced increase in gluconeogenesis is due to increased substrate supply and to hepatic extraction efficiency under certain circumstances, which is comparable to the situation in man.

Effect of insulin on gluconeogenesis and the metabolism of lactate in sheep.

Owing to the fermentative nature of their digestion, ruminant animals are highly dependent upon gluconeogenesis to meet their glucose needs. The role of hormones in regulating this process is not clear. The purpose of this study was to examine the effect of insulin on the utilization of lactate in glucose synthesis in sheep. The euglycemic model was used in sheep. [U-14C]Lactate and [6-3H]glucose were infused to monitor lactate and glucose fluxes. Hepatic metabolism was measured using radioisotopic and venoarterial concentration difference techniques. Insulin concentrations increased from basal concentrations of 16 +/- 2 to 95 +/- 9 microU/mL. Insulin reduced the net hepatic utilization of lactate (303 +/- 43 vs. 120 +/- 27 mumol/min), hepatic extraction efficiency of lactate (29 +/- 4 vs. 9 +/- 2%), hepatic output of glucose (338 +/- 33 vs. 103 +/- 21 mumol/min), and incorporation of lactate into glucose (90 +/- 5 vs. 46 +/- 8 mumol/min). Insulin at physiological levels can inhibit hepatic gluconeogenesis in ruminants.

Effects of growth hormone on glucose and acetate metabolism in sheep.

The effect of intravenous infusion of growth hormone (GH) on glucose metabolism in sheep was determined. To maintain low levels of insulin somatostatin was infused with and without GH. The infusion of GH for 6 hr was without effect on glucose metabolism.

Role of insulin in regulating hepatic gluconeogenesis in sheep.

Ruminant animals, as a result of the fermentative nature of their digestion, ordinarily absorb little or no hexose sugar from the gut. Their glucose needs must be met by gluconeogenesis, even postprandially. The role of insulin in regulating hepatic gluconeogenesis in ruminants has not been assessed. In this study the effect of insulin on net hepatic removal of the major glucose precursors was determined. Insulin was infused with glucose matched to maintain euglycemia. The insulin concentrations attained in plasma were within the physiological range. Insulin at low concentrations reduced the hepatic removal of lactate, glutamine, and glycerol. At higher concentrations of insulin the hepatic extractions of pyruvate and alanine were also reduced. Thus, in sheep insulin at physiological concentrations may reduce hepatic glucose output by altering the uptake of glucose precursors.

Effect of phentolamine on the insulin, glucagon, and glucose responses to exercise in adrenal-denervated sheep.

Hyperglycemia and increased hepatic glucose output are characteristic responses to exercise in sheep. They appear to be due in part to alpha-adrenergic stimulation. To delineate the contributions of sympathetic innervation and adrenal catecholamines to the hormonal and metabolic responses to exercise, adrenal-denervated sheep were exercised with and without alpha-blockade (phentolamine treatment). Alpha blockade exaggerated the hyperinsulinemia during exercise (increment of 61 +/- 8 vs. 34 +/- 7 microU/mL for the control). This was associated with a reduction in glucose appearance (increments of 63 +/- 8 vs. 236 +/- 23 mumol/min, respectively). The metabolic clearance rates were not altered by alpha-blockade. It appears that both the adrenal catecholamines and adrenergic innervation to the pancreas contribute to the prevention of a rise in insulin concentrations during exercise in sheep. While this may not be essential for glucose appearance to rise during exercise, it appears necessary for an optimal response.

Effects of insulin on net hepatic metabolism of acetate and beta-hydroxybutyrate in sheep (Ovis aries).

The net productions of acetate and beta-hydroxybutyrate by the liver and portal-drained viscera were determined before and during insulin plus glucose infusions. Glucose was infused at rates to maintain euglycemia. During insulin infusion the net hepatic productions of beta-hydroxybutyrate and acetate were reduced to a greater extent than could be accounted for by a reduction in provision of free fatty acids to the liver. It is concluded that insulin has a direct anti-ketogenic effect on the ovine liver.

Effects of insulin on the metabolism of acetate, beta-hydroxybutyrate and triglycerides by the bovine mammary gland.

The effect of insulin on net metabolism of acetate, beta-hydroxybutyrate, glucose and triglycerides by the bovine mammary gland was determined using the glucose clamp technique. Elevation of insulin concentrations in plasma by 50 microU/ml was not associated with significant changes in venoarterial concentration differences and extraction ratios ((A-V)/A). Insulin does not appear to alter the metabolism of acetate, beta-hydroxybutyrate, glucose and triglycerides by direct effects on the mammary gland.

The agricultural use of municipal sewage.

The reuse of municipal sewage for agricultural purposes is becoming more prevalent. The literature concerning the impact of this practice is reviewed. It is readily apparent that agricultural reuse of municipal sewage is preferable to other common methods of disposal both from the point of view of ecological influence and economical waste utilization. There is a need to establish guidelines for the agricultural use of municipal sewage which will serve the variable conditions found in Canada and meet the public health concerns associated with an extensive agricultural use.

Effect of glycemic changes on lipolysis in sheep in vivo.

The purpose of this study was to evaluate the effects of glycemic changes on lipolysis in sheep. To prevent hyperglycemia from altering insulin concentrations and hypoglycemia from altering adrenomedullary hormonal secretion, the experiments were conducted in insulin-treated alloxan diabetic sheep whose adrenal glands were denervated. Hyperglycemia was associated with a reduction in glycerol concentrations and hypoglycemia with elevated glycerol. These changes in glycerol concentrations were independent of changes in plasma insulin, glucagon, catecholamine, and cortisol concentrations. It appears that change in glucose concentrations per se can alter lipolysis in sheep.

Validation of an equation for calculation of glucose appearance during nonsteady state in sheep.

The purpose of this study was to validate the calculation of the rate of glucose appearance (RA) during nonsteady state for sheep. The RA given by the modified single-compartment model was compared with the actual rate derived from the sum of the infusion of exogenous glucose and endogenous production as determined from hepatic production of glucose. Using a pool fraction of 0.65, the error associated with calculation of RA was about 10%.

Effects of glucagon, insulin, propionate, acetate, and HCO3 on K excretion in sheep.

The effects on renal K excretion of 1 h intravenous infusion of glucagon, insulin, Na propionate, Na acetate, or NaHCO3 were studied in mature, conscious fasted ewes. These treatments were compared with the fasted state without treatment (control) and with feeding a single daily meal. Renal K excretion was increased by feeding and by Na propionate and Na acetate treatments but not by infusion of glucagon, insulin, and NaHCO3. Since hormone levels were elevated more by specific hormone infusions than by feeding or Na propionate infusions, these results do not support a role for glucagon and insulin in mediating the increases in renal K excretion that occurred after meals or during acetate and propionate infusions. The mechanisms responsible for the acetate- and propionate-induced kaliuresis are not clear but do not appear to include changes in plasma K (PK), glucagon, and insulin (Pinsulin) or in urine flow and urine Na excretion. However, a relation between insulin and K was observed during infusion of KCl in fasting sheep. Above a PK threshold of 4 meq/l, Pinsulin (ng/ml) = 1.52 PK (meq/l) - 5.89. In other experiments, K excretion increased after an intravenous bolus injection of 1 mg of glucagon, indicating that sheep, like humans and dogs, respond to pharmacologic doses of glucagon with kaliuresis.

The effect of hyperglycaemia on the rates of appearance and metabolic clearance of glucose in sheep (Ovis aries).

Glucose appearance and utilization before and during glucose infusions were examined in insulin treated alloxan-diabetic (ITA) and intact sheep. During hyperglycaemia in ITA sheep glucose appearance was reduced to 35% of the preinfusion values whereas in intact sheep it was 17% of preinfusion values. Hyperglycaemia per se appears to inhibit glucose appearance. The utilization of glucose was not proportional to glucose concentrations in ITA sheep, but was in intact sheep where insulin concentrations increased during hyperglycaemia.

Effects of insulin and glucose on the production and utilization of glucose in sheep (Ovis aries).

1. The rates of appearance (RA) and metabolic clearance rates (MCR) of glucose were determined during the infusion of insulin plus glucose in sheep. 2. During euglycaemia 50% inhibition of RA of endogenous glucose occurred at insulin concentrations of 60 microU/ml in arterial plasma. 3. During euglycaemia the MCR of glucose doubled with an increment of about 100 microU/ml of insulin. 4. Hypoglycaemia was associated with a reduction in insulin's suppression of RA of endogenous glucose and hyperglycaemia significantly reduced the increase in MCR due to insulin.

Effect of adrenal denervation on the glucose, insulin, and glucagon responses to exercise in sheep.

Previous studies suggest that adrenal catecholamines mediate, in part, the glucose and pancreatic hormonal responses to exercise in sheep. This was examined in sheep whose adrenals were denervated to prevent stress-induced changes in catecholamine secretion. The innervation to the right adrenal gland was severed and the left adrenal was removed. Adrenal denervation was associated with a reduction in exercise-induced hyperglycemia and impairment, as measured by [2-3H]glucose, of the increase in glucose appearance during the first 10 min of exercise and increased metabolic clearance rate of glucose after 20 min of exercise. Insulin concentrations were significantly higher during exercise after adrenal denervation than in the controls. Adrenal denervation did not alter the rise in glucagon due to exercise. These effects are consistent with adrenomedullary hormonal stimulation of hepatic and muscular glycogenolysis, either directly or indirectly through the regulation of insulin secretion during exercise in sheep.

Effect of adrenergic drugs on glucose and plasma glucagon and insulin responses to xylazine in sheep.

Xylazine was administered intravenously (0.16 mg/kg) to sheep. This was associated with a transient hyperglucagonaemia, hypoinsulinaemia and hyperglycaemia. The rate of glucose appearance as determined by isotope dilution techniques was increased three to four fold during the first 20 minutes after xylazine administration. Phentolamine prevented the xylazine-induced increase in the rate of appearance of glucose, and in concentrations of glucose and glucagon in plasma. The insulin response was not altered by phentolamine. Propranolol had no effect on the glucose and hormonal responses due to xylazine. The xylazine-induced effects on glucose metabolism and secretion by glucagon and insulin appear to be mediated by the alpha-adrenoceptors.

Glucose, glucagon, and insulin during adrenergic blockade in exercising sheep.

The interrelationships of glucagon and insulin with the sympathetic system on glucose turnover during exercise were examined in sheep. Six sheep were run for 45 min on a treadmill with and without alpha- and/or beta-adrenergic blockade. The exercise-induced increase in glucose appearance, as assessed by infusion of [2-3H]glucose, was reduced during the first 25 min of exercise by phentolamine administration. The metabolic clearance rate of glucose also was greater during exercise with phentolamine treatment than without. Phentolamine was associated with a rise in insulin concentrations and appeared to delay the exercise-induced rise in glucagon. Propranolol administration had no effect on glucose turnover and plasma glucagon and insulin. Nor did it have any effect on the changes in glucose, insulin, or glucagon induced by phentolamine administration. These observations are consistent with the alpha-adrenergic mediation of the sympathetic influences on insulin and glucagon secretion, which may account in part for the glucose adaptations to exercise in sheep. However, direct affects of circulating catecholamines on and increased stimulation of sympathetic innervation to the liver cannot be ruled out.