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N Nurjhan

Publications and source records attributed to N Nurjhan.

36 records · Page 2Linked to original sources
PubMed1990

Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration.

It has been proposed that increased supply of gluconeogenic precursors may be largely responsible for the increased gluconeogenesis which contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). Therefore, to test the hypothesis that an increase in gluconeogenic substrate supply per se could increase hepatic glucose output sufficiently to cause fasting hyperglycemia, we infused normal volunteers with sodium lactate at a rate approximately double the rate of appearance observed in NIDDM while clamping plasma insulin, glucagon, and growth hormone at basal levels. In control experiments, sodium bicarbonate was infused instead of sodium lactate at equimolar rates. In both experiments, [6-3H]-glucose was infused to measure glucose appearance and either [U-14C]lactate or [U-14C]alanine was infused to measure the rates of appearance and conversion of these substrates into plasma glucose. Plasma insulin, glucagon, growth hormone, C-peptide, and glycerol concentrations, and blood bicarbonate and pH in control and lactate infusion experiments were not significantly different. Infusion of lactate increased plasma lactate and alanine to 4.48 +/- 3 mM and 610 +/- 33 microM, respectively, from baseline values of 1.6 +/- 0.2 mM and 431 +/- 28 microM, both P less than 0.01; lactate and alanine rates of appearance increased to 38 +/- 1.0 and 8.0 +/- 0.3 mumol/kg per min (P less than 0.01 versus basal rates of 14.4 +/- 0.4 and 5.0 +/- 0.5 mumol/kg per min, respectively). With correction for Krebs cycle carbon exchange, lactate incorporation into plasma glucose increased nearly threefold to 10.4 mumol/kg per min and accounted for about 50% of overall glucose appearance. Alanine incorporation into plasma glucose increased more than twofold. Despite this marked increase in gluconeogenesis, neither overall hepatic glucose output nor plasma glucose increased and each was not significantly different from values observed in control experiments (10.8 +/- 0.5 vs. 10.8 +/- 0.5 mumol/kg per min and 5.4 +/- 0.4 vs. 5.3 +/- 0.3 mM, respectively). We, therefore, conclude that in normal humans there is an autoregulatory process independent of changes in plasma glucose and glucoregulatory hormone concentrations which prevents a substrate-induced increase in gluconeogenesis from increasing overall hepatic glucose output; since this process cannot be explained on the basis of inhibition of gluconeogenesis from other substrates, it probably involves diminution of glycogenolysis. A defect in this process could explain at least in part the increased hepatic glucose output found in NIDDM.

Alanine↗
PubMed1990

Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism.

To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver.

Alanine↗
PubMed1990

Impaired hepatic glycogenolysis related to hyperinsulinemia in newborns from hyperglycemic pregnant rats.

We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.

Animals↗
PubMed1990

Fasting hyperglycemia normalizes oxidative and nonoxidative pathways of insulin-stimulated glucose metabolism in noninsulin-dependent diabetes mellitus.

The present studies were undertaken to determine whether fasting hyperglycemia can compensate for decreased insulin-stimulated glucose disposal, oxidation, and storage in noninsulin-dependent diabetes mellitus (NIDDM) as well as to determine whether hyperglycemia normalizes insulin-stimulated skeletal muscle glycogen synthase and pyruvate dehydrogenase (PDH) activities. To accomplish this, we used the glucose clamp technique with isotopic determination of glucose disposal and indirect calorimetry for measuring the pathways of glucose metabolism, and vastus lateralis muscle biopsies to determine the effects of insulin on glycogen synthase and PDH activities. Nine patients with NIDDM and eight matched non-diabetic subjects were infused with insulin (40 mU/m2.min) while plasma glucose was maintained at the prevailing fasting concentration. During insulin infusion, rates of glucose disposal, storage, and oxidation were the same in the two groups. Insulin infusion significantly activated glycogen synthase fractional velocity to the same extent in NIDDM (0.210 +/- 0.056 vs. 0.332 +/- 0.079) and controls (0.192 +/- 0.036 vs. 0.294 +/- 0.050). Insulin infusion increased PDH fractional velocity in controls (from 0.281 +/- 0.022 to 0.404 +/- 0.038), but not in NIDDM (from 0.356 +/- 0.043 to 0.436 +/- 0.060), although the activity of PDH during insulin infusion did not differ between the groups. We conclude that prevailing fasting hyperglycemia normalizes the nonoxidative and oxidative pathways of insulin-stimulated glucose in metabolism in NIDDM and may act as a homeostatic mechanism to normalize muscle glucose metabolism.

Diabetes Mellitus, Type 2↗
PubMed1990

Contribution of impaired muscle glucose clearance to reduced postabsorptive systemic glucose clearance in NIDDM.

The reduced postabsorptive rates of systemic glucose clearance in non-insulin-dependent diabetes mellitus (NIDDM) are thought to be the consequence of insulin resistance in peripheral tissues. Although the peripheral tissues involved have not been identified, it is generally assumed to be primarily muscle, the major site of insulin-mediated glucose disposal. To test this hypothesis, we measured postabsorptive systemic and forearm glucose utilization and clearance in 15 volunteers with NIDDM and 15 age- and weight-matched nondiabetic volunteers. Although systemic glucose utilization was increased in NIDDM subjects (14.5 +/- 0.5 vs. 11.2 +/- 0.2 mumol.kg-1.min-1, P less than 0.001), systemic glucose clearance was reduced 1.40 +/- 0.06 vs. 2.13 +/- 0.05 ml.kg-1.min-1, P less than 0.01). Although forearm glucose utilization was increased in NIDDM subjects (0.663 +/- 0.058 vs. 0.411 +/- 0.019 mumol.dl-1.min-1, P less than 0.001), forearm glucose dl-1 clearance was reduced (0.628 +/- 0.044 vs. 0.774 +/- 0.037 ml.L-1.min-1, P less than 0.01). However, extrapolation of forearm data to total-body muscle indicated that impaired clearance reduced muscle glucose disposal by only 61 +/- 21 mumol/min, whereas impaired systemic clearance reduced systemic glucose disposal by 662 +/- 82 mumol/min. Thus, impaired muscle glucose clearance accounted for less than 10% of the reduced systemic glucose clearance in NIDDM subjects. Therefore, we conclude that muscle insulin resistance plays only a minor role in the reduced systemic glucose clearance found in NIDDM in the postabsorptive state and propose that reduced brain glucose clearance is largely responsible.

Blood Glucose↗
PubMed1990

Contribution of gluconeogenesis to overall glucose output in diabetic and nondiabetic men.

Increased hepatic glucose output is the main cause of fasting hyperglycemia in non-insulin dependent diabetes mellitus. Due to difficulties in obtaining a quantitative estimate of gluconeogenesis in vivo, the relative contribution of gluconeogenesis and glycogenolysis to this increased hepatic glucose output was unknown. The application in vivo of a new isotopic approach based on a mathematical model of the Krebs cycle enabled us to obtain a quantitative estimate of gluconeogenesis in vivo. Using this approach, gluconeogenesis was found to account for approximately 28% and approximately 97% of overall hepatic glucose output in healthy volunteers in the postabsorptive and in the fasted state respectively. When this technique was used to compare gluconeogenesis rates in non-insulin dependent diabetes mellitus and nondiabetic patients, gluconeogenesis was found to be increased threefold in the patients with non-insulin dependent diabetes mellitus (12.7 +/- 1.6 mu vs 3.6 +/- 0.6 mumol/Kg/min) and to be significantly correlated with fasting plasma glucose. Furthermore, the increase in gluconeogenesis could explain more than 80% of the increase in overall hepatic glucose output in patients with non-insulin dependent diabetes mellitus. In conclusion, in non-insulin dependent diabetes mellitus, gluconeogenesis, as measured by a new isotopic technique, is increased and this increase represents the main cause for increased overall hepatic glucose output and fasting hyperglycemia.

Carbon Radioisotopes↗
PubMed1989

Insulin inhibition of overnight glucose production and gluconeogenesis from lactate in NIDDM.

Increased gluconeogenesis contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). We examined whether insulin inhibits gluconeogenesis from lactate by altering the fate of lactate and/or by reducing lactate flux. Seven patients with NIDDM (age 51 +/- 4 yr, body mass index 28 +/- 2 kg/m2) were studied before and 3 wk after achieving normoglycemia with evening insulin therapy. Basal glucose production (Ra) and utilization were measured overnight [( 3-3H]glucose infusion from 9 P.M. to 8 A.M.) and lactate turnover and conversion to glucose between 4 and 8 A.M. [( U-14C]lactate infusion) before and after insulin therapy. During insulin therapy, fasting plasma glucose decreased from 188 +/- 13 to 99 +/- 7 mg/dl (P less than 0.001) due to inhibition of glucose Ra from 3.0 +/- 0.1 to 2.2 +/- 0.1 mumol.kg-1.min-1 (P less than 0.005). Plasma free insulin increased from 6 +/- 1 to 11 +/- 1 microU/ml (P less than 0.005). Plasma lactate concentrations (1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmol/l before vs. after insulin therapy) and the lactate turnover rate (15.6 +/- 0.9 vs. 14.2 +/- 0.8 mumol.kg.min) remained unchanged, whereas the amount of glucose formed from lactate decreased from 2.0 +/- 0.1 to 1.4 +/- 0.2 mumol.kg-1.min-1 (P less than 0.02) and the percent of lactate turnover converted to glucose decreased from 26 +/- 1 to 20 +/- 2% (P less than 0.05). We conclude that insulin inhibits overnight glucose Ra from lactate by decreasing the proportion of lactate diverted towards gluconeogenesis rather than by altering lactate availability or total flux.

Adult↗
PubMed1989

Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM.

Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.7 +/- 1.0 vs. 12.0 +/- 0.6 mumol.kg-1.min-1 in the nondiabetic volunteers, P less than .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 +/- 1.4 vs. 3.6 +/- 0.4 mumol.kg-1.min-1 in the nondiabetic subjects, P less than .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P less than .05). The increased phosphoenolpyruvate gluconeogenesis accounted for 89 +/- 6% of the increase in overall hepatic glucose output in the NIDDM subjects and was significantly correlated with the fasting plasma glucose concentrations (r = .67, P less than .01). Glycogenolysis, calculated as the difference between overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis, was not significantly different in the NIDDM subjects (9.9 +/- 0.06 mumol.kg-1.min-1) and the nondiabetic volunteers (8.4 +/- 0.3 mumol.kg-1.min-1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.

Adult↗
PubMed1989

Mechanism for underestimation of isotopically determined glucose disposal.

Use of [3H]glucose and a one-compartment model to determine glucose kinetics frequently underestimates the rate of glucose production (Ra). To assess to what extent an isotope effect, a tracer contaminant, or inadequacy of the model was responsible, we measured glucose Ra and forearm clearance of tracer and unlabeled glucose at various concentrations of plasma insulin (approximately 50, approximately 160, and approximately 1800 microU/ml) and plasma glucose (approximately 90, approximately 160, approximately 250, and approximately 400 mg/dl) under steady-state and non-steady-state conditions. Under isotopic steady-state conditions, the clearances of tracer and unlabeled glucose across the forearm were identical, and exogenous glucose infusion rates did not differ significantly from the isotopically determined glucose Ra (10.0 +/- 1.3 vs. 10.5 +/- 1.0 mg.kg-1 fat-free mass.min-1, respectively). However, under isotopic non-steady-state conditions, the isotopically determined Ra was significantly lower than the glucose infusion rate (11.5 +/- 1.3 vs. 13.7 +/- 1.5 mg.kg-1 fat-free mass.min-1, respectively, P less than .001), and the underestimation was related to the deviation from the isotopic steady state. When [3H]glucose specific activity of plasma samples from experiments with the greatest underestimation of Ra was determined by high-performance liquid chromatography, less than 7% of the underestimation could be accounted for by a contaminant. These results indicate that inadequacy of the one-compartment model is responsible for underestimation of glucose Ra under non-steady-state conditions and that there is no detectable isotopic effect or appreciable contaminant of [3-3H]glucose. We conclude that under isotopic steady-state conditions, [3-3H]glucose is a reliable tracer for glucose kinetic studies in humans.

Adult↗
PubMed1989

Isotopic estimation of plasma glucose conversion to plasma lactate using [6-3H]glucose and [6-14C]glucose.

To determine whether [6-3H]glucose could be used to quantitatively estimate the rate of plasma glucose conversion to plasma lactate, we compared the relative transfer of [3H] and [14C]plasma glucose to plasma lactate in nine postabsorptive anesthetized rats infused to isotopic steady state with [6-3H]glucose and [6-14C]glucose. Glucose turnover (mumol/kg/min) measured with [6-3H]glucose (29.4 +/- 1.7) and [6-14C]glucose (25.0 +/- 1.5), Cori cycle activity (4.35 +/- 0.79), and the percentage of plasma lactate derived from plasma glucose calculated from 14C-specific activities (59.8 +/- 5.8) were all comparable to previously reported values for the overnight fasted rat. Although the percentage of plasma lactate derived from plasma glucose calculated from 3H-specific activities (30.0 +/- 3.3) was only half that calculated from 14C-specific activities (P less than 0.001), the 3H:14C ratios were constant over a wide range of percentage of lactate derived from glucose (r = 0.95, P less than 0.001). We conclude that 3H-specific activity ratios of plasma lactate to plasma glucose cannot be directly used as a quantitative estimate of the percentage of plasma lactate derived from plasma glucose; however, correction for the apparent constant proportionality of detritiation of lactate relative to 14C loss could permit use of [6-3H]glucose for this purpose.

Animals↗
PubMed1989

Rates of appearance and disappearance of plasma lactate after oral glucose: implications for indirect-pathway hepatic glycogen repletion in man.

3-14C-lactate and 6-3H-glucose were infused to determine rates of plasma lactate appearance (Ra), disappearance (Rd) and conversion to plasma glucose following ingestion of 75 g glucose in 10 healthy volunteers. Lactate Ra (mumol/kg/min) increased from 10.2 +/- 0.9 to a peak of 15.7 +/- 0.8 at 60 min (p less than 0.01). Lactate Rd increased from 10.2 +/- 0.9 to a peak of 15.9 +/- 4.2 at 120 min (p less than 0.001). During the 3-hour experiment, 15.0 +/- 1.1 g of lactate appeared in plasma, and 14.1 +/- 1.2 g disappeared from plasma. Of lactate Rd, approximately 20% (2.8 +/- 0.2 g) was converted to plasma glucose leaving a maximum 11.3 +/- 0.8 g lactate available for indirect-pathway glycogen synthesis. The present data indicate that in man the indirect pathway could account for about 40% of hepatic glycogen repletion via uptake of circulating gluconeogenic precursors.

Adult↗
PubMed1988

Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo.

To assess whether plasma glycerol could be directly derived from plasma glucose, nine postabsorptive dogs were infused with [U-14C] glucose and [2-3H] glycerol to measure the rates of appearance of plasma glucose and glycerol and the conversion of plasma glucose to glycerol before (basal) and after two hours of infusion of glucose (45 mumol/kg/min). Basally (plasma glucose 4.9 +/- 0.2 mmol/L; plasma insulin 5.9 +/- 0.2 microU/mL), rates of appearance of plasma glucose and glycerol were 20 +/- 2 and 5.9 +/- 1.3 mumol/kg/min, respectively, and 1.6 +/- 0.6% of plasma glycerol was derived from plasma glucose. After glucose infusion (plasma glucose 9.1 +/- 0.7 mmol/L; plasma insulin 21.1 +/- 1.9 microU/mL), the rate of appearance of plasma glycerol decreased 80% to 1.1 +/- 0.3 mumol/kg/min and the percent of plasma glycerol from glucose increased significantly to 6.9 +/- 2.9. However, the absolute rate of conversion of glucose to glycerol did not change (0.09 +/- 0.03 v 0.07 +/- 0.03 mumol/kg/min). We conclude that even under conditions of stimulated glycolysis and inhibited lipolysis, only a small amount of plasma glycerol is derived from plasma glucose. Thus, rates of appearance of plasma glycerol can be used as a measure of rates of overall lipolysis in vivo.

Animals↗
PubMed1986

Insulin dose-response characteristics for suppression of glycerol release and conversion to glucose in humans.

To compare the dose-response characteristics for suppression of lipolysis and suppression of glucose production by insulin, 13 normal nonobese individuals were infused with insulin at rates of 0.1, 0.2, 0.4, 0.8, and 1.6 mU X kg-1 X min-1 while normoglycemia was maintained with the glucose clamp technique. Glucose appearance and glycerol appearance (taken as index of lipolysis) were measured isotopically with simultaneous infusions of 3-[3H]glucose and U-[14C]glycerol. Baseline glucose and glycerol rates of appearance were 14 +/- 0.5 and 1.7 +/- 0.2 mumol X kg-1 X min-1, respectively. Approximately 3% of plasma glucose originated from glycerol, and this accounted for approximately 50% of glycerol disposal. During the insulin infusions, arterial insulin (basal, 9.8 +/- 0.6 microU/ml) increased to 14 +/- 0.5, 20 +/- 0.5, 31 +/- 1, 58 +/- 2, and 104 +/- 6 microU/ml; calculated portal venous insulin (basal, 24 +/- 2 microU/ml) increased to 26 +/- 1, 32 +/- 3, 70 +/- 4, and 115 +/- 6 microU/ml. The rate of glucose appearance was suppressed 100%, whereas the rate of appearance of glycerol was maximally suppressed only 85%. Nevertheless, the insulin concentration that produced half-maximal suppression of glucose appearance was twice as great as that required for half-maximal suppression of glycerol appearance (26 +/- 2 vs. 13 +/- 2 microU/ml, P less than .001). Insulin decreased both the absolute rate of glycerol conversion to plasma glucose and the percent of glycerol disposal appearing in plasma glucose (both P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Insulin and glucagon during the perinatal period: secretion and metabolic effects on the liver.

Insulin and glucagon are detected in the plasma of most species early in gestation. In the fetus at term, insulin and glucagon secretion can be modified by long-term changes in glucose concentration but the responsiveness of A and B cells to glucose is lower than in the adult. The plasma insulin/glucagon molar ratio is high in the fetus at term, then decreases dramatically immediately after birth and remains low during the first hours of extrauterine life. This situation results in favored hepatic glycogen storage and prevented gluconeogenesis in utero, and sharp glycogen breakdown and active gluconeogenesis during the early postnatal period.

Animals↗
PubMed1985

Effects of gestational hyperglycemia on glucose metabolism and its hormonal control in the fasted, newborn rat during the early postnatal period.

To evaluate the effects of gestational hyperglycemia on glucose metabolism and its regulation in the fasted rat during the early postnatal period, unrestrained rats were continuously infused with glucose during the last week of pregnancy. Control rats were infused with distilled water. Newborns were studied during the first six postnatal hours. At birth, newborns from glucose-infused rats, compared with controls, showed higher plasma glucose levels, increased plasma insulin, and lower plasma glucagon and catecholamine concentrations. Between birth and 2 h postpartum, newborn rats from both groups exhibited a marked hypoglycemia, which was, however, more severe in newborns from glucose-infused rats (15 mg/dl) than in controls (26 mg/dl). During the first four postnatal hours, plasma insulin concentration remained higher, while plasma glucagon and catecholamine concentrations remained lower in newborns from hyperglycemic rats. At 6 h, the glycemia reached normal values and the concentrations of the different hormones were similar in controls and newborns from glucose-infused mothers. Concurrently, in the newborns from glucose-infused rats, hepatic glucose production was altered, as they were unable to mobilize liver glycogen stores during the six postnatal hours. Despite slightly delayed phosphoenolpyruvate carboxykinase induction, the rate of gluconeogenesis from 10 mmol/L lactate estimated on isolated hepatocytes was higher in newborns from hyperglycemic mothers than in controls. These results show that gestational hyperglycemia compromises the metabolic and hormonal adaptation of the newborn rat to early extrauterine life; the striking feature of these neonates is the absence of mobilization of liver glycogen stores, which can probably be explained by fetal and neonatal hyperinsulinism associated with the defect of counterregulatory hormones.

Age Factors↗
PubMed1983

Hyperglycaemia induced by glucose infusion in the unrestrained pregnant rat: effect on body weight and lipid synthesis in post-mature fetuses.

Mild hyperglycaemia was induced in unrestrained pregnant rats from day 20.5 to day 23.5 of pregnancy, using a continuous glucose infusion. Control rats were infused with distilled water. In post-mature fetuses from glucose-infused rats, raised plasma glucose and insulin concentrations were related to increased body weight (6.03 +/- 0.07 g) and total carcass fat (2.02 +/- 0.04% of fresh weight) compared with control fetuses of the same age (5.35 +/- 0.07 and 1.5 +/- 0.04 g, respectively). Concurrently, the rate of lipogenesis in the carcass, estimated from the incorporation of tritium from tritiated water into fatty acids, was significantly increased in fetuses from glucose infused rats compared with control rats (6.00 +/- 0.34 versus 2.62 +/- 0.27 and 3H2O X h-1 X g tissue-1, respectively.

Animals↗
PubMed1983

[Maternal hyperglycemia and fetal development in the rat: effects of a continuous glucose perfusion in the rat at the end of gestation].

Continuous glucose infusion was used to induce mild hyperglycemia in unrestrained pregnant rats during the last three days of pregnancy. Control rats were infused with distilled water. Compared with the controls, fetuses from glucose-infused rats showed higher plasma glucose levels, increased plasma insulin and lower plasma glucagon concentrations. Pregnancy prolonged until day 23.5 resulted in a sharp decrease in plasma insulin concentrations and a dramatic increase in plasma glucagon concentrations. In 23.5-day old fetuses from both groups, plasma insulin concentration rose when phentolamine was injected but not when propanolol was injected. Plasma glucagon concentration in 23.5-day old fetuses from glucose-infused rats dropped with propanolol injection. In fetuses from control rats, liver phosphoenolpyruvate activity increased markedly and liver glycogen stores decreased sharply. In fetuses from glucose-infused rats, liver phosphoenolpyruvate carboxykinase activity rose and glycogen content decreased, but to a lesser degree. Moreover, in postmature fetuses from glucose-infused rats, elevated plasma glucose and insulin concentrations were related to increased body weight and total carcass fat. Concurrently, the rate of lipogenesis in the carcass of these fetuses (estimated from the incorporation of 3H from 3H2O into fatty acids) was significantly increased.

Animals↗