Glucose and fatty acid kinetics in fasted rats: Effects of previous protein intake

Glucose and fatty acid turnover and oxidation were measured in 48 hr fasted adult rats who had been previously fed two isocaloric diets of 5% and 18% protein content for 29 days. Kinetics were investigated with the simultaneous primed constant infusions of 6-³H glucose, U-¹⁴C glucose and 1-¹³C palmitic acid. Plasma glucose concentration and glucose turnover were reduced while plasma fatty acid concentration and turnover were increased in the rats fed the 5% protein diet. The protein:carbohydrate ratio of a previous diet affects both glucose and lipid metabolism in adult rats who are fasted.     

Turnover and recycling of glucose in man during prolonged fasting

The effect of prolonged (3–5 wk) fasting on tracer-determined glucose turnover and of recycling radioactive glucose has been examined. We followed the specific activity of plasma glucose after the simultaneous administration of 1-¹⁴C-glucose and 3-³H-glucose. The rate of glucose turnover decreased during prolonged fasting. Recycling of radioactive glucose was estimated by two different techniques: (1) the appearance of ¹⁴C in positions 2 to 6 glucose was measured; (2) the difference in the slopes of specific activity decline for 1-¹⁴C-glucose and for 3-³H-glucose was calculated. The two methods of estimating the radioactive recycling gave results similar to each other. The amount of glucose recycled did not change during prolonged fasting. However, in view of the decline in glucose production during fasting, the proportion of glucose production which was represented by recycling increased. Based on weight and urinary nitrogen loss an estimate of the glucose production from amino acids and glycerol was obtained. The difference between the rate of glucose production from the contribution of amino acids and glycerol and that estimated by radioisotopic techniques was much larger than the measured rate of recycling. This finding suggests that either a large exchange of ¹²C with ¹⁴C occurred in some glycolytic intermediates or that a hitherto unknown source of carbon for glucose production appeared during prolonged fasting.     

Reversible and irreversible glucose disposal in dogs: Influence of fasting and cold exposure

Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25°C) or cold (?21°C) ambient temperatures. A mixture of U ¹⁴C-glucose and 2-³H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.     

Altered mechanism of glucagon-mediated hepatic glycogenolysis during long-term starvation in the rat.

The effect of long-term starvation on glucagon-mediated hepatic glycogenolysis was investigated in the rat in vivo. Following glucagon (50 microgram/kg i.v.) fed rats showed rapid phosphorylase activation but no change in synthase-I activities. In contrast, rats fasted 72 hr (long-term fasting) showed rapid synthase inactivation but no significant phosphorylase activation. Rats fasted 24 hr (short-term fasting) demonstrated coordinated inactivation of synthase and activation of phosphorylase. Hepatic cyclic AMP responses were greater in fasted rats. Hepatic glycogen concentrations in rats fasted 72 hr were approximately 30% of fed levels. After glucagon, comparable decrements in hepatic glycogen and increments in plasma glucose concentrations were seen in fed and 72-hr groups. The diminished responsiveness of the hepatic phosphorylase system in rats fasted 72 hr was not attributable to altered cyclic AMP-dependent protein kinase or phosphorylase kinase activities. However, the diminished responsiveness could be ascribed to diminished total phosphorylase with nearly complete activation in the basal state. In fed and fasted rats, synthase decrements after glucagon correlated closely with basal levels of synthase-I. Thus, it is proposed that the enzymatic mechanism of glucagon-mediated hepatic glycogenolysis differs in fed and fasted rats. It is also proposed that partial hepatic glycogen reaccumulation during long-term fasting could be physiologically important for glucose homeostasis.     

The effects of two years of mestranol treatment on carbohydrate metabolism

Twenty-nine menstrual age women who had a hysterectomy and oophorectomy were treated cyclically with 80 μg of mestranol per day for 2 yr. Their carbohydrate metabolism was evaluated prospectively by doing a 3 hr oral glucose olerance test after a 100 g glucose load and measuring both blood glucose and plasma insulin levels. The tests were performed before drug treatment and after 2 yr of drug use. Those women that had a “normal” predrug test had some carbohydrate metabolism changes at the 2 yr test with significant elevations of the fasting, 1 and 2 hr blood glucose values, and also significant elevations of the 2 and 3 hr plasma insulin values. Those women with a “borderline abnormal” predrug test had no significant change in either parameter of carbohydrate metabolism however a trend toward similar changes was noted.     

In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat

Changes in protein metabolism 8 hr after anesthesia and femur fracture were studied in healthy rats fasted or receiving either intravenous glucose or crystalline amino acids. Whole body rates of amino acid turnover (flux) and release from protein (breakdown) as well as fractional synthetic rates of mixed muscle, liver, and plasma protein were measured using the constant infusion of L-(I-¹⁴C)-leucine. Injury resulted in a 24% and 63% increase in the synthesis of liver (p < 0.05) and plasma proteins (p < 0.01), respectively. Amino acid infusions in the injured animals further increased the synthesis of liver protein (from 36.6% to 44.3%/day, p < 0.05) and increased muscle protein synthesis (from 7.0% to 9.3%/day, p < 0.05) without altering rates of protein breakdown. Glucose infusions, in contrast, reduced whole body protein breakdown 36% (p < 0.05) when compared to fasting, and depleted the plasma essential amino acid pool (p < 0.05). The usual increases in liver protein synthesis observed in fasted rats following injury were not seen when the animals were receiving intravenous glucose. The nitrogen-sparing mechanism of these two infusions are different. Protein-free glucose infusions impair the normal response to injury aimed at increasing visceral protein synthesis and maintaining plasma essential amino acid concentrations.     

The effect of enteric galactose on neonatal canine carbohydrate metabolism

Newborn pups were assigned to a fasting group or to a group receiving intravenous glucose alimentation. Glucose turnover was determined during steady state equilibration of simultaneously infused [6-³H] glucose. Thereafter, pups from each group received 0.625 g/Kg of either oral [U-¹⁴C] galactose or [U-¹⁴C] glucose. In fasted or intravenously alimented pups enteric glucose resulted in a rapid and sustained elevation of blood glucose concentrations. Systemic appearance of carbon-14 label from enteric glucose increased rapidly as did the enrichment of blood [¹⁴C] glucose specific activity. In those pups given enteric galactose, blood glucose values were equivalent to that in the glucose fed groups, however carbon-14 appearing in blood glucose and blood glucose specific activity were significantly lower. The peak values for the rates of appearance and disappearance of systemic glucose were significantly lower in pups fed galactose than among pups fed glucose. Glucose clearance was also significantly lower in these pups despite equivalent plasma insulin responses. Among fasting pups hepatic glycogen content was significantly higher in those given either oral glucose or galactose when compared to a completely starved control group. In contrast, among alimented pups galactose administration significantly enhanced hepatic glycogen content compared to those fed glucose. Similarly, enteric substrate label incorporation into hepatic glycogen was enhanced in both groups given oral labeled galactose. In addition, hepatic glycogen synthase (glucose-6-phosphate independent) activity was increased only among alimented pups fed galactose when compared to completely fasted pups. In conclusion these data suggest that following gastrointestinal galactose administration, hepatic carbohydrate uptake is augmented while glycogen synthesis may be enhanced. Augmented glycogen synthesis following galactose administration may reflect alterations in hepatic glycogen synthase activity or enhanced hepatic carbohydrate uptake.     

Carbohydrate metabolism in pregnancy. XIV. Relationships between circulating glucagon,insulin, glucose and amino acids in response to a “mixed meal” in late pregnancy

Gestational influences upon the changes in circulating glucose, amino acids, insulin, and glucagon after the ingestion of a “mixed meal” containing carbohydrate (50 g), protein (25 g), and fat (10 g) were examined. Nine subjects were tested during weeks 30–40 of gestation and again 6–8 wk postpartum. The “mixed meal” elicited greater and more prolonged increases in plasma glucose antepartum, whereas the increments in total serum amino acids were blunted at all time points. In the face of greater glycemic but lesser aminogenic stimulation, the integrated increase in plasma insulin was 60% greater antepartum than post partum, whereas the increment in glucagon was not significantly altered. Thus, integrated insulin/glucagon response was increased during antepartum studies. The insulin preponderance following alimentary challenge with mixed nutrients would suggest that the anabolism of ingested amino acids is “facilitated” during late human pregnancy.     

Effects of glycogen stores and non-esterified fatty acid availability on insulin-stimulated glucose metabolism and tissue pyruvate dehydrogenase activity in the rat

Summary The effects of increased tissue glycogen stores on insulin sensitivity, and on the response of insulin-stimulated glucose utilisation to an acute elevation in plasma fatty acid levels (1.5mmol/l), were investigated in conscious rats using the hyperinsulinaemic euglycaemic clamp. Studies were performed in two groups of rats; (a) fasted 24 h; (b) fasted 4.5 h, but infused with glucose for 4 h (0.5 g/h) of this period before the clamp (fed, glucose infused rats). Clamp glucose requirement and 3-³H-glucose turnover were 20–25% lower in the fed, glucose-infused rats. In these rats, elevation of plasma fatty acid levels resulted in impaired suppression of hepatic glucose output (residual hepatic glucose output: 41±4 vs 8±6 mol·min^–1·kg^–1. p < 0.001) but did not further decrease 3-³H-glucose turnover. Elevated nonesterified fatty acid levels had no significant effect on glucose kinetics in 24 h fasted rats. In the fed glucose-infused rats, at low plasma fatty acid levels, there was no deposition of glycogen in muscle during the clamp and liver glycogen levels fell. With elevation of non-esterified fatty acid levels muscle glycogen deposition was stimulated in both groups, and there was no fall in liver glycogen during the clamps in the fed glucose-infused rats. Increased non-esterified fatty acid availability during the clamps decreased pyruvate dehydrogenase activity in liver, heart, adipose tissue and quadriceps muscle, in both groups of rats. The findings are consistent with an inhibition of glycolysis in liver, skeletal muscle and heart by increased fatty acid availability. Increased glycogen synthesis, however, compensates for decreased glycolytic flux so that glucose turnover is not decreased. When liver glycogen stores are high, an acute increase in non-esterified fatty acid availability impairs suppression of hepatic glucose output. A chronic increase in non-esteriefid fatty acid availability may lead to insulin resistance by increasing glycogen stores.     

Blood D-3-hydroxybutyrate and the regulation of plasma concentrations of free fatty acids in the fasted rat.

Acetoacetate or DL-3-hydroxybutyrate were infused into fasted rats at rates comparable to the endogenous rate of ketone body release. Blood samples taken before and during infusion were analyzed for concentrations of ketone bodies, free fatty acids, and immunoreactive insulin. During infusion of acetoacetate or DL-3-hydroxybutyrate, blood concentrations of total ketone bodies doubled. While the HBA/AcAc ratios remained constant in rats infused with DL-3-hydroxybutyrate, the ratios decreased significantly during infusion of acetoacetate, reflecting increases in acetoacetate concentrations without proportionate increases in concentrations of D-3-hydroxybutyrate. Blood concentrations of free fatty acids decreased more rapidly in the rats infused with DL-3-hydroxybutyrate than in the rats infused with acetoacetate. The decrease in free fatty acid concentrations was related to increases in blood D-3-hydroxybutyrate in both the DL-3-hydroxybutyrate-infused rats and in the acetoacetate-infused rats. Plasma immunoreactive insulin concentrations were significantly higher in the DL-3-hydroxybutyrate-infused rats than in the acetoacetate-infused rats. Acetoacetate and DL-3-hydroxybutyrate were infused into depancreatized, functionally hepatectomized fasted rats at rates comparable to those used in the intact fasted rats. Only small decreases in free fatty acid concentrations were observed during infusion. From these experiments it was concluded that increases in blood concentrations of D-3-hydroxybutyrate were more effective than acetoacetate in causing decreases in free fatty acid concentrations in the fasting rat. The pancreas is required for this effect.     

Influence of nicotinic acid on the rates of turnover and oxidation of plasma glucose in man

The effects of antilipolysis induced by nicotinic acid on the rates of turnover and oxidation of plasma glucose were studied in normal overnight fasted, obese overnight fasted, and obese starved subjects, using a ¹⁴C-glucose infusion technique. Changes induced by nicotinic acid were similar whatever the nutritional state of the subjects. Plasma FFA levels and blood concentrations of glycerol and ketones decreased by about 60%; glycemia remained essentially unchanged but both the removal rate of plasma glucose and the hepatic glucose output increased by about 25%. Moreover, the fraction of glucose taken up by tissues and promptly oxidized and the fraction of expired CO₂ derived from plasma glucose increased, respectively, by 18% and 33%. This enhancement of glucose utilization occurred despite a small but significant decrease in plasma IRI concentration, indicating that nicotinic acid increased sensitivity to insulin. The above-mentioned results were obtained in 8 of the 10 patients studied. The remaining two subjects did not respond to the administration of nicotinic acid by any significant decrease in FFA nor in glycerol concentrations and showed no change in the rates of glucose turnover and oxidation. These data indicate that the effects of nicotinic acid on glucose metabolism may be partly mediated through changes in plasma FFA concentration and are consistent with the idea that the “glucose-fatty acid cycle” plays a significant role in the control of glucose metabolism in man.     

Effects of ethanol on glucose turnover in pregnant rats

Glucose turnover was measured in term pregnant rats fed ethanol (30% of caloric intake) throughout gestation. Ethanol ingestion significantly reduced maternal weight gain and term fetal body weight when compared to pair-fed or ad libitum-fed controls. At term the blood glucose level and 6-3H-glucose turnover were reduced when compared to either control group. The rate of gluconeogenic recycling, indicated by the difference between 6-3H and 6-14C-glucose turnover determinations, was reduced by ethanol ingestion to half that of the control groups. Glucose turnover correlated with both conceptus weight and blood glucose level. Impaired maternal glucose homeostasis, including a reduced gluconeogenic response to the metabolic demands of late pregnancy, may thus contribute to the effects of ethanol on intrauterine growth.     

Preservation of glucose tolerance and insulin secretory response to repeated glucose loads by the feeding of minimal glucose during prolonged fasting

The facilitation of glucose disposal (Staub-Traugott effect) and potentiation of serum insulin (IRI) concentration normally occurring after closely spaced intravenous glucose loads, are known to disappear after prolonged starvation. To study the effects of minimal amounts of glucose during fasting upon the insulin response and disposal of repeated intravenous glucose tolerance tests, obese volunteers were fasted for a mean of 25 ± 2 days, while receiving either 8 or 16 gm of oral glucose every 6 hr, and compared to totally fasted subjects without glucose supplementation. Weight loss rate and the fall in basal IRI and glucose levels were similar to those of totally fasted subjects. However, the Staub-Traugott effect and insulin secretory dynamics after stimulation by repetitive intravenous glucose loading were preserved by this glucose modified fast, while baseline serum glucagon levels (IRG) were significantly lower, and the basal IRI/IRG ratios were thus unchanged from the fed state. IRG and free fatty acid suppression were similar in the fed and glucose modified fasted states. Lactic acid levels increased as expected after the repeated glucose injections in the fed state, but failed to do so after the prolonged modified fast until the second and third repetitive glucose loads, in which a significant rise coincided with accelerated glucose disposal. It is suggested that minimal amounts of carbohydrate during fasting preserve the insulin potentiating action of glucose, preferentially sparing a delayed releasable pool of insulin, while protecting the glucose utilization mechanisms, including increased glycolysis, responsible for the Staub-Traugott effect.     

Potentiation of 14C-glucose oxidation by priming glucose loads: Effect of starvation

The mechanism of the Staub-Traugott effect or facilitated glucose disposal after successive glucose loads has remained elusive. In earlier publications, we have shown it can be independent of circulating hormone and free fatty acid levels. We have also proposed that it might partially depend on the rapid induction of glycogytic pathways, which are known to be depressed by prolonged fast. Mature rats were given 1.75 gm/kg glucose doses intravenously at 60-minute intervals. Respiratory CO₂ was collected at 15-minute intervals over a 120-minute period following administration of the carrier glucose plus $\text{6 μ}\text{Ci}\text{100 gm}$ rat weight of ¹⁴C-d-glucose, given either as the first, second, or third challenge. In rats fasted 14 hours there was potentiation of labeled CO₂ recovered after each successive load. After three days of starvation, both relative ¹⁴C-glucose oxidation to ¹⁴CO₂ as well as absolute ¹⁴CO₂ increments after each load were lower. The changes in relative oxidation of an intravenous glucose load might partly account for the facilitated disposal of blood glucose seen in the second and third hours in overnight-fasted rats (Staub-Traugott effect). However, although rats fasted for three days had suppressed the Staub effect, the increments in oxidation were attenuated but still present, suggesting that alterations of other pathways must participate in the disappearance of this effect after fasting.     

Development of fasting hyperglycemia in uremic rats

Rats which had been fasted for the previous 24 hr were subjected to either sham surgery, bilateral nephrectomy, or bilateral ureterotomy. The fast was continued for another 24 hr before the animals were decapitated and blood was obtained for determination of serum glucose, insulin, and urea nitrogen levels. A moderate but statistically significant (p < 0.02) fall in serum glucose levels occurred in rats made uremic by bilateral nephrectomy. In contrast, rats made equally uremic by bilateral ureterotomy developed a significant (p < 0.001) elevation of both serum glucose and insulin levels. The combination of hyperglycemia and hyperinsulinemia suggested that insulin resistance had developed in these rats, and this was confirmed by demonstrating that the hypoglycemic effect of exogenously administered insulin was attenuated in rats following bilateral ureterotomy as compared to sham-operated rats. Unilateral ureterotomy did not lead to the same metabolic response, and the difference in serum glucose levels between sham-operated and bilaterally ureterotomized rats disappeared when a 5% glucose solution was substituted for tap water as the rat's drinking water. It is suggested that the coexistence of fasting and metabolic acidosis led to increased renal gluconeogenesis in rats subjected to bilateral ureterotomy, and the combination of increased renal glucose production and insulin resistance was responsible for the development of fasting hyperglycemia.     

Hepatic insulin and glucagon receptors in pregnancy: their role in the enhanced catabolism during fasting

The response to dietary deprivation in late pregnancy, as compared to the non-pregnant condition, is more rapid and profound in terms of mobilization of fuels frm peripheral tissues as well as hepatic ketogenesis and gluconeogenesis ("accelerated starvation"). We examined the potential role of hepatic insulin and glucagon receptors in mediating these changes by comparing 48-h fasted 18-day pregnant and age-matched nongravid rats. Molar ratios for insulin:glucagon in peripheral and portal blood were significantly higher in the pregnant rats. Insulin binding to purified liver plasma membrane receptors, when appropriately corrected for differences in insulin degradation by the membrane system, was marginally diminished in the pregnant animals. Glucagon binding and adenylate cyclase activation by glucagon was indistinguishable in the two groups of animals. On the basis of portal vein hormone concentrations and the values for receptor binding, liver insulinization relative to glucagonization appears to be unchanged or slightly increased in the fasted pregnant rat compared to the fasted nongravid rat. Thus, it seems unlikely that much of the "accelerated starvation" response in late pregnancy can be ascribed to diminished insulin and/or increased glucagon availability at the hepatocellular level. Instead, it is hypothesized that postreceptor events play the major role in sustaining the intrahepatic realignments of established fasting in late pregnancy.     

Initial splanchnic extraction of ingested glucose in normal man

Estimates of initial splanchnic uptake of ingested glucose and the concomitant suppression of endogenous glucose production were obtained in man by validated tracer techniques for non-steady-state turnover measurement. Nine normal volunteers (18–44 yr old) fasted overnight received intravenous infusions of tracer (3-³H-glucose or 1-¹⁴C-glucose) and a low (45 ± 1 g) or high (96 ± 5 g) oral load of glucose labeled with an alternative tracer (1-¹⁴C-glucose or 2-³H-glucose). A two-compartment model was used to derive rates of peripheral appearance (Ra) of glucose from all sources (total) and the Ra of ingested glucose. Ra (total glucose) and Ra (ingested glucose) were integrated from the first appearance of ingested glucose until the basal Ra (total glucose) of 116 ± 6 (SEM) mg/min was reattained. The total amount of glucose reaching the systemic pool in this time was 95 ± 4 g and 46 ± 3 g with high and low doses, respectively. Of these quantities 86 ± 4 g and 40 ± 3 g originated in the oral glucose, representing 90% ± 4% of the administered glucose. The remainder (11% ± 2% of the total) represented endogenous production, suppressed by 66% ± 6% relative to basal. Sequestration of ingested glucose and subsequent release did not take place during the study since identical results were obtained with ingested 1-¹⁴C-glucose or 2-³H-glucose. The latter label would have been lost if the glucose had entered the hexose-phosphate pool. Thus, in normal man approximately 90% of an ingested glucose load is absorbed and passes through the liver to appear in the systemic pool.     

Effect of starvation on hepatic glycogen metabolism and glucose homeostasis.

The effects of starvation on the hepatic glycogen synthase and phosphporylase systems were sequentially assessed in fed and 24-120-hr-fasted rats. Enzymic changes before and after glucose were correlated with simultaneous measurements of hepatic cyclic AMP and glycogen concentrations and glucose, insulin, and glucagon concentrations in the portal vein plasma. Fasting caused parallel changes in plasma glucose and hepatic glycogen concentrations with decreases by 24 hr and subsequent increases, which correlated with increases in hepatic synthase l and decreases in phosphorylase activites. Hepatic cyclic AMP levels increased as 24-48 hr, decreased below fed levels at 96 hr, and increased again at 120 hr. Fasting caused progressive impairment of glucose disposal, decreased basal and postglucose insulin concentrations, and decreased basal glucagon levels at 48-72 hr. Hepatic synthase l increments following glucose were exaggerated in 48-120-hr-fasted rats, although consistent phosphorylase decrements were seen only in fed rats. There was no clearcut relationship between synthase activation and phosphorylase inactivation following glucose in fed or fasted rats.     

Metabolism of urea and glucose in normal and diabetic pregnancy

Quantitative estimation of rates of urea synthesis, urea and nitrogen excretion and glucose production were done in ten normal, seven insulin-dependent diabetic and three gestationally diabetic subjects, after an overnight fast during the third trimester of pregnancy. Studies were repeated on three normal, three insulin-dependent diabetic, and two gestationally diabetic subjects during postpartum. [¹⁵N₂]urea and [6,6-²H₂]glucose tracers were infused simultaneously at constant rate for five hours from 12–17 hr of fasting. Plasma [¹⁵N₂]urea and [²H₂] glucose enrichments were measured by gas chromatograph-mass spectrometry. Rates of urea synthesis and glucose production were estimated during steady state by tracer dilution. Overnight fast resulted in a decline in plasma glucose. Extension of the fast by another 5 hr resulted in a further decrease in the levels of circulating glucose and rise in the level of betahydroxybutyrate in both normal and diabetic pregnant subjects. There was no significant difference in the plasma concentration of amino acids after 12 hr of overnight fast, between the normal and diabetic subjects during antepartum. However, a significant increase in the plasma concentration of amino acids occurred during the postpartum period. The plasma urea nitrogen concentration was reduced by 60% during antepartum period (8.22 ± 2.24 and 11.49 ± 3.16 mg/dl; mean ± SD). There was a corresponding decrease in the rate of urea nitrogen synthesis (4.17 ± 1.28 and 6.84 ± 2.52 mg/kg hr). In addition, the rates of urinary urea nitrogen and total nitrogen excretion were attenuated during pregnancy. In contrast, the ammonia excretion rate remained unchanged (0.24 ± 0.09 versus 0.23 ± 0.12 mg/kg hr) in the antepartum and postpartum period. Rigorous regulation of diabetes in pregnancy resulted in normalization of urea and glucose metabolism after an overnight fast. The plasma glucose concentration was reduced during pregnancy, while the rate of glucose production expressed per unit body weight was unchanged. The decreased urea synthesis rate during pregnancy resulted in an altered relationship between urea and glucose production rates. These data suggest conservation of amino nitrogen during pregnancy in humans, apparently for tissue protein synthesis. As ureogenesis is a concomitant of gluconeogenesis from amino acids, these data further suggest an attenuated hepatic gluconeogenesis following a brief 17 hr fast. The mechanism of these observations appears to be via decreased delivery of substrate to the liver for ureogenesis possibly as a result of diversion to the fetus.     

Increased glucose carbon recycling in severely insulin deficient Type 1 (insulin-dependent) diabetic subjects

Summary Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-¹⁴C-glucose and 3-³H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69±0.23 to 1.11±0.21 mmol/l (mean±SEM, p<0.05), total ketones from 0.27±0.06 to 2.06±0.51 mmol/l (p<0.01), cortisol from 341±43 to 479±31 nmol/l (p<0.05) and growth hormone from 1.1±0.3 to 19+5-mu/l (p<0.05). Glucose turnover rose from 13.8±2.3 mol·kg^–1·min^–1 at a glucose of 6.9±0.7 mmol/l in the insulin infused study to 25.8±4.4 mol·kg^–1·min^–1 (p<0.05) at a glucose of 16.4±0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0±0.4 mol· kg^–1·min^–1 to 9.4±2.2 mol·kg^–1·min^–1 (p<0.05) when insulin withdrawn, accounting for 23±3% and 36±3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production.