Effect of reduced inspired oxygen on fetal growth and maternal glucose metabolism in rat pregnancy.

The effect of prolonged exposure to a reduced fraction of inspired oxygen ([FiO2] 0.17 for 3 days) on maternal glucose kinetics, placental glucose transporters GLUT1 and GLUT3, and fetal growth was examined in rat pregnancy. Arterial and venous catheters were placed 3 days before the study. [3-(3)H]glucose tracer and deuterium labeling of water were used to measure the rates of glucose turnover and gluconeogenesis (GNG), respectively. Glucose uptake by maternal tissues was measured using [14C]2-deoxyglucose. Exposure to a reduced FiO2 resulted in a significant decrease (mean +/- SE) in fetal weight (room air, 4.02 +/- 0.04 g; 0.17 FiO2, 3.27 +/- 0.6 g, P < .02). There was a significant increase in the maternal-fetal glucose gradient (maternal-fetal glucose ratio: room air, 1.48 +/- 0.11; 0.17 FiO2, 2.26 +/- 0.24, P < .05), but there was no change in the maternal or fetal blood lactate concentration. No significant change in maternal blood pH was observed; however, a significant decrease in the blood partial pressure of O2 (PO2) occurred (room air, 97 +/- 0.5 torr; 0.17 FiO2, 81 +/- 1.8) on day 3. There was no change in the rate of turnover of glucose or GNG in the maternal compartment, nor was there any effect on glucose uptake by the maternal tissues. Placental GLUT1 and GLUT3 mRNA were not different in the control or experimental animals. We conclude that a mild reduction in the FiO2 for 3 days in rat pregnancy results in a significant fetal growth restriction that is not related to any observed alteration in maternal glucose metabolism. The lower glucose concentration in the fetal blood may be the consequence of an increase in fetal glucose metabolism, thereby resulting in an increased maternal-fetal gradient of glucose.     

The effect of ethanol on glucose production in phosphorylase b kinase deficiency

Summary Glucose production was measured using stable isotopic techniques in two patients with phosphorylase b kinase deficiency before and after oral ethanol (0.75 g/kg). Glucose production was normal before the ethanol. In one patient, who did not take the full dose of ethanol, glucose production rose initially and then fell. In the other, glucose production fell steadily and in both patients blood lactate concentrations rose. Blood glucose concentrations decreased.Patients with this enzyme deficiency are dependent on the gluconeogenic pathway when fasting and, therefore, ethanol may be potentially hazardous.     

Carbohydrate dynamics in the hypermetabolic septic rat

Glucose turnover is increased during shock and in acute sepsis, but relatively little information is available concerning the regulation of carbohydrate metabolism during the hypermetabolic phase of sepsis. In these studies peritoneal sepsis was induced in rats, following chronic vascular catheterization, by intraperitoneal administration of a pooled fecal inoculum. The resultant peritonitis has been shown to produce a sustained hypermetabolic state during the first three days of infection. Glucose and lactate kinetics were studied using a constant infusion of radiolabeled tracers during the peak of the hypermetabolic phase (day 2). The septic animals exhibited a 42% increase in glucose turnover and a 63% increase in the metabolic clearance rate of glucose, as compared to time-matched control rats. Hepatic glycogenolysis could only contribute 1% to 2% to the increased rate of glucose appearance. A major portion of the elevated glucose turnover was accounted for by a 93% increase in glucose recycling, indicating an enhancement of gluconeogenesis from glucose-derived gluconeogenic precursors. The increased importance of lactate as a precursor for gluconeogenesis in sepsis was indicated by the elevated lactate turnover (34%) and the increased percentage of 14C-glucose derived from 14C-lactate. The insulin to glucagon ratio was decreased in the septic animals as a result of a reduction in the plasma insulin concentration (56%) and an increased glucagon concentration (67%). We conclude that during the hypermetabolic phase of sepsis, the increased peripheral glucose uptake generated more gluconeogenic precursors but did not appear to have a major direct contribution to the increased aerobic metabolism.     

Fetal Alcohol Syndrome: Glucose and Liver Metabolism in Term Rat Fetus and Neonate

The combined effects of chronic ethanol ingestion and fasting (24-hr fast, except water, prior to delivery) were examined in term pregnant rats and their offspring. Rats fed liquid diet containing 5% (w/v) ethanol (EF) consumed fewer calories than those fed control diet and exhibited reduced weight gain relative to either ad libitum-fed (AF) or pair-fed (PF) controls. While the number of live fetuses at term was unaffected, fetal body and liver weights were reduced in EF litters. Blood glucose levels were significantly lower in EF fetuses although maternal glucose levels did not differ between the groups. Liver glycogen levels also were reduced in EF fetuses, without any change in plasma immunoreactive insulin or immunoreactive glucagon levels. Both active and total glycogen synthase and phosphorylase were significantly lower in livers of EF fetuses than in livers of control fetuses. After delivery, blood glucose and plasma immunoreactive insulin levels fell more slowly in EF neonates than in either control group, but EF neonates remained hypoglycemic at 4 hr postnatal, whereas glycemia in both control groups had recovered to normal. Plasma immunoreactive glucagon levels in EF were elevated during the first 2 hr following delivery relative to either AF or PF controls, and hepatic glycogen levels were reduced in EF neonates during the entire interval studied. Conclusion: Fetal exposure to ethanol in utero and to a short maternal fasting prior to delivery results in fetal growth retardation, hypoglycemia, hypoinsulinemia, and liver glycogen depletion at term. Also, both glycogen synthase (active and total) and phosphorylase (active and total) were decreased as well.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring

Epidemiologic studies have demonstrated associations between low birth weight and increased rates of adult diseases such as hypertension and diabetes. Maternal iron restriction in the rat has been reported to both reduce birth weight and to elevate blood pressure at 40 days of age. The aim of the present study was to extend these findings to investigate the effects of maternal iron restriction on glucose tolerance and serum lipids, 2 important components of the metabolic syndrome, in adult offspring. Blood pressure, glucose tolerance, and serum lipids were measured in the 3-month-old offspring of iron-restricted dams. Rats were placed on control or iron-restricted diets 1 week before mating. At term, dams on the iron-restricted diet were anemic with decreased haemoglobin, red blood cell (RBC) count, hematocrit, and mean RBC volume compared with controls. Neonates from iron-restricted litters were more severely anemic than the dams. At birth, body weight was lower in the offspring of iron-restricted dams than in controls and was still decreased at 3 months of age. At this same age, systolic blood pressure was significantly elevated in the offspring of iron-restricted dams. Glucose tolerance was improved in the maternal iron-restricted group. Fasting serum insulin levels were not different between the control and maternal iron-restricted groups. Fasting serum triglyceride was decreased in the offspring of iron-restricted dams compared with controls. Fasting serum cholesterol and free fatty acid concentrations were similar in both groups. These results suggest that maternal iron restriction has long-term effects on physiology and metabolism in the offspring. Some of these findings are comparable to those reported for the maternal protein-restriction model. It is thus speculated that the long-term effects of maternal dietary restriction may result from common fetal metabolic responses to this restriction.     

Dietary and exercise interventions and glycemic control and maternal and newborn outcomes in women diagnosed with gestational diabetes: Systematic review

Gestational diabetes mellitus (GDM) is one of the most common complication of pregnancy and can lead to significant perinatal mortalities as well as long term risk of comorbidities for both mother and her offspring. This systematic review aimed to explore whether combined diet and exercise interventions are associated with improved glycemic control and/or improved maternal and newborn outcomes in women with GDM when compared to dietary interventions. A search on combined diet and exercise interventions during pregnancy in women with GDM was performed in 3 electronic databases: PubMed (NCBI), ScienceDierct, and the Cochrane Library. Evaluated outcomes were fasting blood glucose levels, postprandial blood glucose levels, glycated hemoglobin percentages, total weight gain during pregnancy, proportion of caesarean delivery, proportion of patients needing insulin, neonatal birth weight, proportion of macrosomia, neonatal hypoglycemia, and preterm birth. This systematic review identified eight randomized, controlled trials involving 592 pregnant women and 350 infants. The risk of bias of the included trials ranged from high to low. The combined diet and exercise interventions reduced fasting and postprandial blood glucose levels when compared to dietary interventions. No significant differences were reported in the selected trials regarding total weight gain during pregnancy, cesarean section, neonatal birth weight, macrosomia, neonatal hypoglycemia, and preterm birth between diet plus exercise and diet groups. The combination of diet and exercise interventions help to control postprandial blood glucose concentration in women diagnosed with GDM, but did not change either maternal or newborn outcomes.RegistrationPROSPERO CRD42018109896.     

Influence of glucose, alcohol and glycerol on galactose tolerance in man

Six volunteers were given 0.5 g galactose/kg body weight alone (A) or with 0.5 g glucose/kg (B) or with 0.5 g glycerol/kg body weight (C). Meals A and B were also given 15 min after ingestion of 300 mg ethanol/kg body weight. Glycerol did not influence the serum galactose response to galactose. Glucose reduced the serum galactose response as was expected. Administration of alcohol prior to a galactose test meal increased the mean area under the serum galactose response curve (p less than 0.01); when glucose was given with galactose after alcohol ingestion, the serum galactose response was significantly reduced (p less than 0.01) when compared to the serum galactose response to galactose after alcohol, but remained higher than after the galactose and glucose test meal. Glucose, therefore, can reduce the effect of alcohol on galactose levels but alcohol can abolish the effect of glucose on galactose metabolism.     

Carbohydrate metabolism in pregnancy XVI: Longitudinal estimates of the effects of pregnancy on D-(63H) glucose and D-(6-14C) glucose turnovers during fasting in the rat

We measured blood glucose concentrations and glucose turnover rates in 24 hr fasted, conscious, unrestrained pregnant rats and nongravid controls on days 18, 19, and 20 of gestation. Turnover measurements were secured with simultaneous equilibrium infusions of D-(6-³H) and D-(6-¹⁴C) glucose so that gluconeogenic recycling could also be determined. “Steady state” values for blood glucose in the mother after 24 hr of fasting did not significantly differ on each of the days, and these concentrations were significantly lower than the values in 24 hr fasted nongravid rats. At 18 days gestation, glucose turnover did not differ from nongravid values. By contrast, values for glucose turnover after 24 hr fasting increased significantly and progressively in the 19 and 20 day pregnant rats. The increase in turnover correlated with the increasing growth of the conceptus. The ratio between D-(6-¹⁴C) glucose and D-(6-³H) turnover remained constant (and the same as in the nongravid rats) during all 3 days of gestation suggesting that rates of glucose recycling remained unaltered. These longitudinal studies indicate that the factors contributing to the pattern of “accelerated starvation” during dietary deprivation in pregnancy may vary as pregnancy progresses. The exaggerated lowering of blood glucose which accompanies fasting occurs before total glucose turnover increases. This could provide a potential mechanism for conserving maternal glucose. Since transplacental transfer of glucose is concentration-dependent, the early establishment of a lower “steady state” for circulating glucose could diminish the magnitude of loss of this key nutrient to the fetus.     

Glucose and alanine metabolism during bacterial infections in rats and rhesus monkeys

To investigate the effects of bacterial infection on glucose and alanine metabolism, a variety of studies were carried out in rat and monkey models. These included glucose turnover by a pulse-dose technique in infected rats; alanine and glucose production and utilization in control and septic monkeys; in vivo measurement of gluconeogenesis in rats, with and without an alanine load; the in vitro rate of glucose formation from various substrates by isolated liver perfusion and hepatic cells; and in vivo rates of oxidation of glucose labeled with ¹⁴C at the 1 or 6 carbon position. In rats, glucose turnover was markedly accelerated 24 hr after inoculation of either 10⁴ or 10⁷Streptococcus pneumoniae. Glucose utilization and production were also accelerated during illness and early recovery from a pneumococcal infection in monkeys. The rates of gluconeogenesis as measured by either a pulse technique in rats or continuous infusion of labeled alanine in monkey were significantly elevated during pneumococcal septicemia. During the agonal stages (10⁷) of the pneumococcal infection in rat, an alanine load resulted in a decreased rate of labeled glucose production and an increase in plasma glucose when compared to values of fasted control rats. However, early illness caused similar or increased rates of glucose production from alanine in vivo. Similar reduced rates of glucose formation were observed when the isolated livers or hepatocytes from rats during the agonal stages of infection were perfused with excess quantities of gluconeogenic substrates. Thus, in the rat, gluconeogenic capacity (ability to form glucose from excess substrates) appears to decrease only during the agonal stages of pneumococcal infection. During acute pneumococcal sepsis in the rhesus monkey, alanine production and utilization were significantly elevated and it was estimated that over 90% of the newly produced alanine was utilized for glucose synthesis. When arterial-venous differences were measured across the hindquarters, significantly more alanine was released, presumably from skeletal muscle of the septic monkey, compared to the recovery period or in the control groups. Thus, the increase in glucose synthesis in both rat and monkey appears to be correlated with substrate availability and kinetic rate, rather than gluconeogenic capacity of the liver. The major increase in glucose utilization during both S. pneumoniae and Francisella tularensis live vaccine strain (LVS) infections in rat was a progressive elevation in the rate of oxidation via the pentose phosphate shunt in the rat. Further, the rate of oxidation appeared to be correlated with the magnitude of the bacteremia, which is an indication of the severity of the infection. Therefore, since glucose oxidation is necessary for a number of metabolic processes of various cells (such as phagocytosis and RNA synthesis), the increased glucose production during pneumococcal sepsis in the rat or rhesus monkey may not represent functional wastage to remove the excess alanine produced in skeletal muscle but a necessary process in the host defense mechanism against infectious disease.     

Effect of exogenous insulin on glucose kinetics in rats with noninsulin-dependent diabetes

Noninsulin-dependent diabetes (NIDD) was induced in adult female rats by neonatal administration of streptozotocin. Despite elevated basal plasma glucose values in the postabsorptive state (196 +/- 16 mg/100 mL as compared to 118 +/- 7 in the controls), the glucose disappearance rate measured after the intravenous glucose load was not significantly lower in the diabetic than in control rats. In contrast, in vivo glucose-induced insulin release was drastically reduced, thus suggesting that endogenous insulin was more effective on the target tissues of the diabetic rats. Glucose kinetics (glucose production, utilization, and clearance) in response to intravenous insulin injection were studied in anesthetized postabsorptive diabetic and control female rats using [6-3H] glucose. With a maximal dose of insulin (0.5 U/kg body weight) no difference in blood glucose-lowering effect of insulin was found between the 2 groups. With 2 submaximal insulin doses (0.15 and 0.3 U/kg body weight), glucose production was inhibited more rapidly and more efficiently in diabetic rats than in control rats: 2 minutes after the 0.15 U/kg insulin injection, endogenous glucose production fell by 79 +/- 5% in the diabetics while being unchanged in the controls and the maximal decrease of glucose production after the same insulin injection was significantly greater in the diabetic rats (79 +/- 5% at 2 minutes) compared to the controls (33 +/- 4% at 6 min). The rise of glucose clearance in response to insulin was not significantly different in the 2 groups. These findings are discussed in view of the increased insulin clearance rate in these diabetic females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of hepatic glucose output during moderate exercise in non-insulin-dependent diabetes

In normal subjects during moderate exercise there is a strong negative correlation between plasma glucose and hepatic glucose output (HGO) suggesting a negative feedback regulation of HGO by plasma glucose. Little information is available about HGO responses to exercise in non-insulin-dependent diabetes mellitus (NIDDM). To determine whether the same feedback relationship is operative, we have compared the glucose turnover responses to moderate exercise (50% Vo2max for 60 minutes) of nonobese non-insulin-dependent diabetic subjects (NIDDM, n = 7) with a group of age-matched controls (n = 5). Glucose turnover responses to exercise in NIDDM were heterogeneous. Plasma glucose showed sustained falls, no change, or sustained rises in different individuals. Similarly, HGO responses ranged from undetectable to responses comparable to those of normal subjects. The mean integrated HGO response in NIDDM was significantly reduced compared with controls (11 +/- 6 [SEM] v 33 +/- 7 mmol/h/70 kg, P less than .05); mean glucose utilization response was also reduced but not significantly different from controls (NIDDM 18 +/- 5 v control 35 +/- 6). In NIDDM there was no significant feedback-control relationship between plasma glucose and HGO (r = -0.20, P = NS) in contrast to controls (r = -0.87, P less than .01). We conclude that feedback control of HGO by plasma glucose during moderate exercise is impaired in NIDDM. This impairment may be due to defective nonpancreatic glucoregulatory mechanisms.     

Acute effects of dichloroacetate in the depancreatized dog: Glucose synthesis and turnover

Summary Blood glucose turnover (entry and removal rates) and the rate of recycling of radiolabelled glucose carbon into newly synthesized blood glucose have been evaluated before and acutely after the administration of dichloroacetate to depancreatized dogs. Blood glucose concentration began to decline immediately after dichloracetate administration and fell to new steady state levels within 1.5–3 h. Analysis of blood glucose kinetics during the decline demonstrated a 52% (average) reduction in the rate of hepatic glucose supply. Glucose supply remained reduced over the duration of these studies (3–4.5 h). Glucose turnover in the steady state following dichloroacetate administration averaged 62% of pretreatment values. Cori cycle activity was depressed by 63% after dichloroacetate administration. The results of these studies are consistent with the hypothesis that a major mechanism underlying the hypoglycaemic action of this drug is the inhibition of glucose synthesis.     

妊娠期糖尿病孕妇分娩前糖化血红蛋白与新生儿血糖及出生体重的相关性分析

目的探讨妊娠期糖尿病(GDM)孕妇分娩前糖化血红蛋白(HbA1c)与新生儿血糖及出生体重的相关性。方法选取2018年9月至2020年12月于西南医科大学附属医院分娩的178例GDM孕妇及其新生儿作为研究对象。以分娩前1周内的HbA1c反映GDM孕妇分娩前2~3个月的血糖控制水平,将GDM孕妇分为HbA1c≥6%组(45例)和HbA1c<6%组(133例)。收集新生儿出生体重及出生后早期血糖值作为结局指标。采用Pearson相关分析和Spearman偏相关分析法分析孕妇分娩前HbA1c与新生儿初始血糖的线性相关性,采用多元线性回归模型分析分娩前HbA1c水平与新生儿出生体重的相关性。采用多元logistic回归分析法分析新生儿低血糖和大于胎龄儿(LGA)的发生风险。结果与分娩前HbA1c≥6%组相比,HbA1c<6%组GDM孕妇的新生儿初始血糖更高[分别为(3.5±1.4)和(2.8±1.3)mmol/L,t=2.85,P<0.01]。Pearson相关分析显示,分娩前HbA1c与新生儿初始血糖呈负相关(r=-0.25,P<0.001);采用Spearman偏相关分析控制混杂因素,该负相关关系仍然存在(r=-0.27,P<0.001)。多元线性回归分析结果显示,在排除胎龄等因素的影响后,分娩前HbA1c每降低0.1%,新生儿的出生体重减少24 g(β=24,95%CI 16~33,P<0.001)。将HbA1c以连续变量进入logistic回归模型,调整相关混杂因素后,GDM孕妇分娩前HbA1c每降低0.1%,其新生儿的低血糖发生风险降低12%(OR=0.88,95%CI 0.82~0.95,P<0.001),LGA的发生风险降低8%(OR=0.92,95%CI 0.87~0.97,P<0.01)。将HbA1c以二分类变量进入多元logistic回归模型并调整相关混杂因素,与分娩前HbA1c≥6%组的GDM孕妇相比较,分娩前HbA1c<6%组的GDM孕妇,其子代新生儿低血糖(OR=0.23,95%CI 0.09~0.59)及LGA(OR=0.30,95%CI 0.12~0.71)的发生风险均降低,差异具有统计学意义(均P<0.01)。结论GDM孕妇分娩前HbA1c与新生儿血糖及出生体重相关,良好的血糖控制能显著降低新生儿低血糖及LGA的发生率。     

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.     

Ethanol-Induced Intrauterine Growth Retardation: Correlation with Placental Glucose Transfer

Placental transfer of glucose and alanine analogs was studied at term in ethanol-fed and control rats. Ethanol was provided as 30% of the caloric intake throughout gestation. Control groups received isocaloric liquid diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of pregnancy, the rats were injected with a mixture of [3H]2-deoxyglucose and [14C]alpha-aminoisobutyric acid. The ratios of fetal:maternal plasma radioactivities 1 hr later were used to compare placental transfer between the groups. Mean +/- SE body weight of EF fetuses (4.54 +/- 0.07 g) was significantly lower than that of PF (4.88 +/- 0.06 g) or AF (5.17 +/- 0.09 g) fetuses. Maternal ethanol ingestion reduced placental transfer of 2-deoxyglucose and alpha-aminoisobutyric acid by 12% and 35%, respectively. Placental transfer of both analogs was not affected in the PF controls. The weight of EF fetuses correlated (p less than 0.001) with transfer of 2-deoxyglucose to the fetus. This relationship was also found in the control groups. Fetal body weight did not show a strong correlation with alpha-aminoisobutyric acid transfer. Thus, impaired transfer of glucose to the fetus may play a significant role in the growth retardation observed in fetuses of ethanol-fed rats.     

The effect of intraperitoneal insulin delivery on carbohydrate metabolism in type 1 (insulin-dependent) diabetic patients.

Patients with type 1 diabetes are usually given insulin subcutaneously, but this does not mimic the physiological route of pancreatic insulin release, which may be better achieved with intraperitoneal insulin. Five C-peptide negative type 1 diabetic patients were studied on two occasions, once with intravenous (IV) and once with intraperitoneal (IP) insulin. Normoglycaemia was maintained from 1700 h with variable insulin infusion, and glucose turnover and recycling assessed from 0600 to 0800 h. A 4-h hyperinsulinaemic (25 mU kg-1 h-1) euglycaemic clamp was then performed, with IP or IV insulin delivery. During the night similar insulin infusion rates were needed to achieve equal blood glucose concentrations. Glucose turnover was identical (IV: 2.4 +/- 0.2 vs IP: 2.3 +/- 0.1 mg kg-1 min-1) (+/- SE) with glucose/carbon recycling 8.8 +/- 4.7 and 12.8 +/- 2.9% (NS). Blood lactate, pyruvate and alanine concentrations were significantly higher with IP than IV insulin (P less than 0.05). During the clamp, insulin concentration was 28 +/- 3 mU/l with IV insulin and 15 +/- 1 mU/l with IP insulin (P less than 0.05) and glucose requirement 2.0 +/- 0.5 and 0.8 +/- 0.3 mg kg-1 min-1, respectively (P less than 0.05). Glucose carbon recycling was higher with IP insulin (P less than 0.05). We conclude that: (1) in type 1 (insulin-dependent) diabetic patients hepatic glucose production could be normalized with both routes of insulin administration, and (2) at the same insulin infusion rate, the relative peripheral hypoinsulinaemia with IP route is sufficient to increase the rate of release of gluconeogenic precursors, or decrease their hepatic uptake.     

Assessment of the postprandial pattern of glucose metabolism in nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus using a simultaneous infusion of [2(3)H] and [3(3)H] glucose

Glucose turnover determined with tritiated isotopes of glucose is subject to potential error due to glucose/glucose-6-phosphate cycling and/or cycling through glycogen. To determine the extent to which these processes alter the apparent pattern of postprandial glucose metabolism, we measured glucose turnover simultaneously with [2(3)H] glucose (an isotope that minimally cycles through glycogen but is extensively detritiated during glucose/glucose-6-phosphate cycling) and [3(3)H] glucose (an isotope that is not detritiated during glucose/glucose-6-phosphate cycling but can cycle through glycogen). Glucose turnover was measured in patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic subjects both before and after ingestion of a carbohydrate meal isotopically with labeled [6(14)C] glucose. In the postabsorptive state hepatic glucose appearance was higher (P less than .05) when determined with [2(3)H] glucose than with [3(3)H] glucose in the diabetic patients, but not in the nondiabetic subjects. After glucose ingestion the integrated responses of glucose appearance, systemic entry of ingested glucose, and hepatic glucose release all were higher (P less than .05) when determined with [2(3)H] glucose compared to [3(3)H] glucose in both the diabetic and nondiabetic subjects. However, the absolute difference between glucose turnover measured with [2(3)H] and [3(3)H] glucose were similar in the diabetic and nondiabetic subjects. Both isotopes provided a similar assessment of postprandial carbohydrate metabolism, indicating that either isotope can be used with equal efficacy to compare postprandial carbohydrate metabolism in patients with NIDDM and nondiabetic subjects.     

Glucose turnover rate and peripheral insulin sensitivity in alcoholic patients without liver damage

Glucose intolerance is frequently found in alcoholic patients and an impaired insulin response has been documented in them. To look for alternative mechanisms that could explain this intolerance, a glucose turnover using tritiated glucose and an euglycemic glucose clamp were performed to measure the glucose production rate and peripheral insulin sensitivity, respectively. Two groups of recently abstinent chronic male alcoholic patients without evidence of liver damage were studied. The glucose turnover technique showed a higher basal glucose production rate in alcoholics, compared with normal volunteers (2.83 +/- 0.29 vs. 1.84 +/- 0.22 mg/kg/min); an intravenous ethanol load significantly increased this rate. The euglycemic glucose clamp did not show peripheral insulin resistance in alcoholics, compared with controls.     

Effects of insulin on glucagon-stimulated glucose production in the conscious dog

The relative importance of insulin and glucagon as primary regulators of glucose metabolism in vivo was assessed in 18-hour fasted conscious dogs. Glucose turnover was determined using [3-3H]glucose and gluconeogenesis was assessed using tracer ([14C]alanine) and A-V difference techniques during a 40-minute control period and a 3-hour period during which various hormonal perturbations were brought about. During the infusion of somatostatin and basal intraportal replacement amounts of insulin and glucagon for the entire study, the plasma glucose concentration (109 +/- 5 mg/dL), glucose production (3.24 +/- 0.30 mg/kg/min), and glucose utilization (3.17 +/- 0.32 mg/kg/min) remained unchanged. When the glucagon infusion rate was increased fourfold at the end of the control period, the plasma glucose level increased from 107 +/- 4 to 225 +/- 23 mg/dL by 1 hour and remained elevated. Glucose production increased from 3.14 +/- 0.29 to 7.66 +/- 0.51 mg/kg/min by 15 minutes and decreased to 4.23 +/- 0.35 mg/kg/min by 3 hours. Glucose utilization rose from a basal value of 3.20 +/- 0.26 to 5.46 +/- 0.27 mg/kg/min by 3 hours. When a fourfold increase in the insulin infusion rate was brought about at the end of the control period, glucose production decreased from 2.83 +/- 0.20 to 1.16 +/- 0.57 mg/kg/min by 1 hour, after which it increased slightly (1.62 +/- 0.81 mg/kg/min). Glucose utilization increased from 2.92 +/- 0.30 to 8.12 +/- 1.12 mg/kg/min by 3 hours. Euglycemia was maintained by glucose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Alcohol on Glucose Tolerance in Normal and Noninsulin-dependent Diabetic Subjects

Oral glucose tolerance tests were conducted in 10 noninsulin-dependent diabetic and 14 healthy control subjects with a 75-g glucose load. The tests were repeated 1 week later with 43 g of ethanol mixed with the glucose. Blood samples were analyzed for ethanol, glucose, insulin, C-peptide, and glucagon levels. The blood ethanol peak was nearly equal in diabetic and control subjects (mean +/- SEM values of 55 +/- 8 and 48 +/- 6 mg/dl 45 min after ethanol ingestion). Ethanol did not affect glucose tolerance in either of the study groups. Mean +/- SEM values of the sum of the increment above the baseline glucose level were 659 +/- 48 vs. 675 +/- 76 mg/dl with or without ethanol in diabetics and 227 +/- 35 vs. 244 +/- 36 mg/dl in control subjects. The plasma insulin and C-peptide responses to glucose were delayed in diabetic patients compared to controls but were not affected by ethanol. In vitro, ethanol, at a concentration of 100 mg/dl or greater, significantly decreased insulin binding to erythrocytes in a dose-related manner. Scatchard analysis of competitive insulin binding to erythrocytes indicated that ethanol reduced insulin binding affinity (1.6 +/- 0.5 vs. 4.2 +/- 0.8 x 10(8)/M), but not binding capacity (4.5 +/- 2.4 vs. 4.4 +/- 1.7 nM, with and without ethanol, respectively).