Biomedical subjects

K Kumaran

Publications and source records attributed to K Kumaran.

At least 19 recordsLinked to original sources

PubMed2006

Relationships of maternal and paternal birthweights to features of the metabolic syndrome in adult offspring: an inter-generational study in South India.

AIMS/HYPOTHESIS: The association between lower birthweight and metabolic syndrome may result from fetal undernutrition (fetal programming hypothesis) and/or genes causing both low birthweight and insulin resistance (fetal insulin hypothesis). We studied associations between the birthweight of parents and metabolic syndrome in the offspring. METHODS: We identified men and women (aged 35-68 years), who had been born in Holdsworth Memorial Hospital, Mysore, India. We also identified the offspring (20-46 years) of these men and women. In total, 283 offspring of 193 mothers and 223 offspring of 144 fathers were studied. Investigations included anthropometry, oral glucose tolerance, plasma insulin and lipid concentrations and blood pressure. The metabolic syndrome was defined using WHO criteria. RESULTS: Among the offspring, lower birthweight was associated with an increased risk of glucose intolerance (impaired glucose tolerance, impaired fasting glucose or type 2 diabetes) and higher cholesterol and triacylglycerol concentrations (p < 0.05 for all adjusted for sex and age). Most outcomes in the offspring, including most individual components of the metabolic syndrome, were unrelated to parental birthweight. However, both maternal and paternal birthweight were inversely related to offspring metabolic syndrome (odds ratio [OR] 0.36 [95% CI: 0.13-1.01] per kg, p = 0.053 for mother-offspring pairs; OR 0.26 [0.07-0.93], p = 0.04 for father-offspring pairs, adjusted for offspring age, sex, BMI and socioeconomic status). Maternal birthweight was inversely related to offspring systolic blood pressure (beta = -2.5 mmHg [-5.00 to 0.03] per kg maternal birthweight; p = 0.052). CONCLUSIONS/INTERPRETATION: Factors in both parents may influence the risk of metabolic syndrome in their offspring. There are several possible explanations, but the findings are consistent with the fetal insulin (genetic) hypothesis.

Adult↗

PubMed2006

Human protein reference database--2006 update.

Human Protein Reference Database (HPRD) (http://www.hprd.org) was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein-protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein-protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (http://www.genprot.org), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data.

Databases, Protein↗

PubMed2004

Intergenerational effects on size at birth in South India.

Several studies have shown that a baby's birthweight correlates with the birthweight and adult size of both its parents, but more strongly with those of its mother, suggesting that both the 'maternal environment' and inherited genes influence size at birth. There are no previous such intergenerational data from India. Holdsworth Memorial Hospital (HMH), Mysore, South India, has preserved birth records containing the birthweight, length and head circumference of all newborns since 1934. We identified 468 mother-offspring and 341 father-offspring pairs born in the hospital. Daughters and sons (born 1990-95) were heavier at birth than their mothers and fathers, respectively, with a mean (SD) increase in birthweight of 121 g (24 g) between the two generations. The birthweight of both parents predicted offspring birthweight equally (mother: regression slope beta = 255 g/kg; father beta = 251 g/kg; P < 0.001 for both). Paternal birth length had a stronger effect than maternal birth length on offspring birth length. The mother's adult body mass index (BMI) had a greater effect than paternal BMI on offspring birthweight (mother: 18 g/kg/m(2); P < 0.001; father: 15 g/kg/m(2); P = 0.04). In a regression model including data for both parents (available for 57 children) this difference was greater (mother: 46 g/kg/m(2); P < 0.001; father: -10 g/kg/m(2); ns). In contrast, paternal height had stronger effects than maternal height on offspring birth length (mother: 0.8 mm/cm; ns; father: 1.5 mm/cm; P < 0.001). In conclusion, size at birth is influenced by a combination of environmental and genetic factors. Both maternal and paternal birthweight correlate with offspring size at birth. Maternal nutritional status (BMI) influences birthweight. Paternal factors appear to contribute to neonatal skeletal size.

Adult↗

PubMed2003

Cortisol and the metabolic syndrome in South Asians.

OBJECTIVE: The cardiovascular risk factors which comprise the metabolic syndrome are associated with increased hypothalamic-pituitary-adrenal axis (HPAA) activity in some Caucasian populations. South Asians have high rates of cardiovascular disease and its risk factors. We have investigated the relationships between HPAA activity, adiposity and the metabolic syndrome in a South Asian population. DESIGN: Cross-sectional cohort study. PARTICIPANTS: A total of 509 men and women born at the Holdsworth Memorial Hospital, Mysore, South India between 1934 and 1954 and still living in the area. MEASUREMENTS: Fasting 09.00 h cortisol and corticosteroid-binding globulin. The cohort had previously been investigated for features of the metabolic syndrome. RESULTS: At 09.00 h, cortisol concentration was strongly associated with systolic and diastolic blood pressure (r = 0.25 and r = 0.24, respectively; P < 0.001), fasting glucose concentration (r = 0.26; P < 0.001), insulin resistance (r = 0.20; P < 0.001) and fasting triglyceride concentration (r = 0.17; P < 0.001). In general, higher cortisol concentrations added to the effect of adiposity in increasing cardiovascular risk factors, but there was evidence of an interaction between cortisol and adiposity in determining fasting glucose concentration (P = 0.045) and insulin resistance (P = 0.006). CONCLUSIONS: Associations between 09.00 h cortisol concentration and cardiovascular risk factors in this South Asian cohort were stronger than those previously shown in Caucasian populations, despite similar mean cortisol concentrations, and were amplified by adiposity. This suggests that increased glucocorticoid action may contribute to ethnic differences in the prevalence of the metabolic syndrome, particularly among men and women with a higher body mass index.

Adult↗

PubMed2002

Left ventricular mass and arterial compliance: relation to coronary heart disease and its risk factors in South Indian adults.

BACKGROUND: Rates of coronary heart disease (CHD) in India are rising, and are now similar to those in Western countries. The prevalence of conventional CHD risk factors such as hypercholesterolaemia, hypertension, smoking and obesity, tend to be lower in Indian than Western populations, and fail to explain these high rates of disease. Increased left ventricular (LV) mass and decreased arterial compliance predict a higher risk of CHD in Western populations, but there are no published data from India. We have measured LV mass and arterial compliance, and examined their relation to CHD and other known risk factors, in men and women living in Mysore, South India. METHODS: We examined 435 men and women born in Mysore during 1934-1953. LV mass was measured by echocardiography and arterial compliance (derived from pulse wave velocity, PWV) was measured by a non-invasive optical method in three arterial segments. RESULTS: The mean LV mass was 149 g (S.D. 37) in men and 125 g (S.D. 32) in women. The mean PWV was 4.14 m/s in the aorto-radial, 3.28 m/s in the aorto-femoral and 13.59 m/s in the femoro-popliteal-posterior tibial segments. LV mass and PWV were positively correlated with each other and with systolic and diastolic blood pressures, non-insulin dependant diabetes mellitus, fasting plasma glucose, insulin, proinsulin concentrations and serum triglyceride concentrations (p<0.05 for all), independently of age, sex and body size. In addition, LV mass correlated negatively with fasting serum HDL-cholesterol (p=0.02). Higher LV mass was associated with an increased risk of CHD (p=0.05). CONCLUSIONS: The mean LV mass in this Indian population is low compared with Western populations, though as in the West, increased LV mass is associated with an increased risk of CHD. Greater LV mass and reduced arterial compliance are associated with higher levels of many known CHD risk factors especially with those which form the Insulin Resistance Syndrome.

Adult↗

PubMed2000

Blood pressure, arterial compliance, and left ventricular mass: no relation to small size at birth in south Indian adults.

OBJECTIVE: To determine whether reduced fetal growth leads to raised blood pressure, reduced arterial compliance, and increased left ventricular mass in an Indian population. DESIGN: A retrospective cohort study of men and women (age range 40-61 years) whose weight, length, and head circumference at birth were recorded. SETTING: The Holdsworth Memorial Hospital, Mysore, South India. SUBJECTS: 435 men and women born in the hospital between 1934 and 1953. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures; compliance in four arterial segments derived from pulse wave velocity, measured by a non-invasive optical method; and left ventricular mass measured using M mode echocardiography. RESULTS: Small size at birth was not associated with increased adult blood pressure or left ventricular mass, or with reduced arterial compliance. Systolic blood pressure and left ventricular mass were higher in subjects who were greater in length at birth, rising by 1.64 mm Hg (95% confidence interval (CI) -0.08 to +3.37 mm Hg) and 1.63 g/m(2) (95% CI 0.13 to 3.13 g/m(2)), respectively, per one inch (2.5 cm) increase in birth length, independently of adult size. Arterial compliance was reduced in people whose mothers were lighter and had smaller pelvic (external conjugate) diameters. CONCLUSIONS: The higher prevalence of coronary heart disease in Indian men and women of lower birth weight, shown in an earlier study of the same cohort, cannot be explained by changes in blood pressure, arterial compliance, and left ventricular mass. The association of raised blood pressure and left ventricular mass with longer birth length suggests that the way in which the intrauterine environment influences coronary heart disease differs between Indian and Western populations.

Adult↗

PubMed1998

Size at birth, maternal weight, and type 2 diabetes in South India.

Recent research in Europe and the USA has shown that adults who had a low birthweight or who were thin at birth with a low ponderal index (birthweight/length3) tend to be insulin resistant and have an increased risk of developing Type 2 diabetes mellitus. Low birthweight and Type 2 diabetes are common in India. We have studied glucose and insulin metabolism in 506 men and women (aged 39-60 years) born in a hospital in Mysore, South India, which kept detailed obstetric records from 1934. The prevalence of Type 2 diabetes was 15%. In contrast to Western populations, higher rates were found in men and women who were short at birth (p = 0.07) and had a high ponderal index (p = 0.05). Their mothers tended to be heavier than average during pregnancy (p = 0.004). Higher ponderal index at birth was also associated with a lower 30 minute insulin increment (p = 0.009), a marker of reduced beta cell function. We speculate that the rise in Type 2 diabetes in Indian urban populations may have been triggered by mild obesity in mothers, leading to glucose intolerance during pregnancy, macrosomic changes in the fetus, and insulin deficiency in adult life.

Adult↗

PubMed1997

Relation of fetal growth to adult lung function in south India.

BACKGROUND: Follow up studies in Britain have shown that low rates of fetal growth are followed by reduced lung function in adult life, independent of smoking and social class. It is suggested that fetal adaptations to undernutrition in utero result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. India has high rates of intrauterine growth retardation, but no study has examined the association between fetal growth and adult lung function in Indian people. We have related size at birth to lung function in an urban Indian population aged 38-59 years. METHODS: Two hundred and eighty six men and women born in one hospital in Mysore City, South India, during 1934-1953 were traced by a house-to-house survey of the city. Their mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured using a turbine spirometer. These measurements were linked to their size at birth, recorded at the time. RESULTS: In both men and women mean FEV1 fell with decreasing birthweight. Adjusted for age and height, it fell by 0.09 litres with each pound (454 g) decrease in birthweight in men (95% confidence interval (CI) 0.01 to 0.16) and by 0.06 (95% CI -0.01 to 0.13) in women. Likewise, mean FVC fell by 0.11 litres (95% CI 0.02 to 0.19) with each pound decrease in birthweight in men, and by 0.08 litres (95% CI 0.002 to 0.16) in women. FEV1 and FVC were lower in men who smoked, but the associations with size at birth were independent of smoking. Small head circumference at birth was associated with a low FEV1/FVC ratio in men which may reflect restriction in airway growth in early gestation. CONCLUSION: This is further evidence that adult lung function is "programmed" in fetal life. Smoking may be particularly detrimental to the lung function of populations already disadvantaged by poor rates of fetal growth.

Adult↗

PubMed1996

Fetal growth and coronary heart disease in south India.

BACKGROUND: Coronary heart disease is predicted to become the commonest cause of death in india within 15 years People from India living overseas already have high rates of the disease that are not explained by known coronary risk factors. Small size at birth is a newly described risk factor for coronary heart disease, but associations between size at birth and the disease have not been examined in India. METHODS: We studied 517 men and women who were born between 1934 and 1954 in a mission hospital in Mysore, South India, and who still lived near to the hospital. We related the prevalence of coronary heart disease, defined by standard criteria, to their birth size. FINDINGS: 25 (9%) men and 27 (11%) women had coronary heart disease. Low birthweight, short birth length, and small head circumference at birth were associated with a raised prevalence of the disease. Prevalence fell from 11% in people whose birthweights were 5.5 lb (2.5 kg) or less to 3% in those whose birthweights were more than 7 lb (3.1 kg), p for trend = 0.09. The trends were stronger and statistically significant among people aged 45 years and over (p = 0.03 for birthweight, 0.04 for length, and 0.02 for head circumference). High rates of disease were also found in those whose mothers had a low body weight during pregnancy. The highest prevalence of the disease (20%) was in people who weighted 5.5 lb (2.5 kg) or less at birth and whose mothers weighted less than 100 lb (45 kg) in pregnancy. These associations were largely independent of known coronary risk factors. INTERPRETATION: In India, as in the UK, coronary heart disease is associated with small size at birth, suggesting that its pathogenesis is influenced by events in utero. The association with low maternal bodyweight is further evidence that the disease originates through fetal undernutrition. Prevention of the rising epidemic of the disease in India may require improvements in the nutrition and health of young women.

Birth Weight↗

PubMed1995

Gluconeogenesis and glucuronidation in liver in vivo and the heterogeneity of hepatocyte function.

In order to examine metabolic zonation in human liver, [2-14C]glycerol, which labels carbons 2 and 5 of glucose-6-P, and [1-14C]lactate, which labels carbons 3 and 4 of glucose-6-P, in the process of gluconeogenesis, were infused intravenously into healthy subjects who ingested acetaminophen and had fasted 36 h. Distributions of 14C were determined in glucose in blood and in the glucuronic acid moiety of acetaminophen glucuronide excreted in urine. Ratios of 14C in carbons 2 and 5 to 14C in carbons 3 and 4 were significantly higher in blood glucose than in glucuronide. Since glucose and glucuronic acid are formed from glucose-6-P in liver without randomization of carbon, the differences in the ratios indicate that the pool of glucose-6-P in liver is not homogeneous. The glucuronide sampled glucose-6-P with more label from lactate than glycerol compared to the glucose-6-P sampled by the glucose. The apparent explanation is the greater decrease in glycerol compared with lactate concentration as blood streams from the periportal to the perivenous zones of the liver lobule. Glucuronidation is then expressed in humans relatively more in the perivenous than periportal zones and gluconeogenesis from glycerol more in the periportal than perivenous zones.

Acetaminophen↗

PubMed1995

Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients.

Normal subjects, fasted 60 h, and patients with insulin-dependent diabetes mellitus (IDDM), withdrawn from insulin and fasted overnight, were given phenylacetate orally and intravenously infused with [3-14C]lactate and 13C-bicarbonate. Rates of hepatic gluconeogenesis relative to Krebs cycle rates were estimated from the 14C distribution in glutamate from urinary phenylacetylglutamine. Assuming the 13C enrichment of breath CO2 was that of the CO2 fixed by pyruvate, the enrichment to be expected in blood glucose, if all hepatic glucose production had been by gluconeogenesis, was then estimated. That estimate was compared with the actual enrichment in blood glucose, yielding the fraction of glucose production due to gluconeogenesis. Relative rates were similar in the 60-h fasted healthy subjects and the diabetic patients. Conversion of oxaloacetate to phosphoenolpyruvate was two to eight times Krebs cycle flux and decarboxylation of pyruvate to acetyl-CoA, oxidized in the cycle, was less than one-30th the fixation by pyruvate of CO2. Thus, in estimating the contribution of a gluconeogenic substrate to glucose production by measuring the incorporation of label from the labelled substrate into glucose, dilution of label at the level of oxaloacetate is relatively small. Pyruvate cycling was as much as one-half the rate of conversion of pyruvate to oxaloacetate. Glucose and glutamate carbons were derived from oxaloacetate formed by similar pathways if not from a common pool. In the 60-h fasted subjects, over 80% of glucose production was via gluconeogenesis. In the diabetic subjects the percentages averaged about 45%.

Adult↗

PubMed1993

Quantitation of the pathways followed in the conversion of fructose to glucose in liver.

Recently, only about 50% of the conversion of fructose to glucose was reported to be via fructose-1-P aldolase catalysis in children. This was also suggested to be the case in adults. That possibility has been tested using a method that quantifies the pathways of fructose conversion to glucose via the fate of 14C from specifically labeled fructose. Trace [6-14C] fructose or its immediate precursor [6-14C]sorbitol with unlabeled fructose (0.3 mg/kg body weight/min) was given intravenously or intragastrically with trace [1-14C]lactate to six normal adults fasted overnight. The distributions of 14C in glucose from blood samples were determined. The ratios of 14C in C1 to C6 of the glucose were equal to or only slightly less than the ratios of 14C in C3 to C4. Since incorporation into C3 and C4 of glucose must have arisen via the conversion of [1-14C]lactate to [1-14C]triose phosphates, fructose conversion to glucose must also have arisen predominantly via the triose phosphates. From the ratios, 85.1% to 100%, a mean of 94.9% of the fructose converted to glucose is calculated to have been converted to glucose with cleavage of the carbon skeleton of the fructose. These findings contrast with the report that in children under similar conditions only about 50% of the conversion of fructose to glucose is with cleavage. The findings agree with previous results in which fructose was administered to normal adults as a bolus at a dose of 60 mg/kg body weight. The possible reasons that the findings in children are different from those in adults are considered.

Adult↗

PubMed1993

14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux.

Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.

Adult↗

PubMed1992

Use of 14CO2 in estimating rates of hepatic gluconeogenesis.

Estimating the rate of hepatic gluconeogenesis in vivo from the incorporation of 14C from 14CO2 into glucose requires determination of the rates in liver of equilibration of oxaloacetate with fumarate, conversion of oxaloacetate to phosphoenolpyruvate (PEP), and conversion of PEP to pyruvate, all relative to the rate of tricarboxylic acid cycle flux. With the use of a model of mitochondrial metabolism and gluconeogenesis, expressions are derived relating specific activity of carboxyl of PEP from 14CO2 to those rates and specific activity of mitochondrial CO2. If those rates and specific activity of mitochondrial CO2 are known, specific activity of PEP, calculated using the expressions, should, on a mole basis, be one-half the specific activity of the glucose formed. At steady state, in the 60-h fasted individual, where glucose formation is solely by gluconeogenesis, twice estimated specific activity of PEP should then approximate that of blood glucose. Estimates of relative rates in 60-h fasted humans, previously made from distribution of 14C in glutamate from phenylacetylglutamine excreted when [3-14C]lactate and phenylacetate were given, were applied to the expressions. Specific activity of mitochondrial CO2 was equated to that of CO2 expired by 60-h fasted subjects given NaH14CO3 and alpha-[1-14C]ketoisocaproate. Predicted specific activities approximated actual specific activities of blood glucose when NaH14CO3 was administered. alpha-[1-14C]ketoisocaproate administrations gave underestimates. This is attributable to differences between specific activities of hepatic mitochondrial CO2 and expired CO2, which is evidenced by higher incorporations of 14C in glucose than in expired CO2 from alpha-[1-14C]ketoisocaproate than from NaH14CO3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Noninvasive tracing of Krebs cycle metabolism in liver.

To quantify intrahepatic Krebs cycle metabolism, phenyl acetate, excreted in urine as a glutamine conjugate, was given to healthy subjects infused with [3-14C]lactate. They were studied after 60 h of fasting and when given glucose after an overnight fast. Distributions of 14C in glutamate from urinary phenylacetylglutamine and blood glucose were determined. Corrections to the distributions because of the fixation of 14CO2 formed from the [3-14C]lactate were determined by administering [14C]bicarbonate. Comparisons of distributions in glucose and glutamate support the assumption that the glutamate distributions reflect those in hepatic alpha-ketoglutarate. From the distributions in glutamate, the extent of exchange of labeled with unlabeled carbons and relative flow rates in the cycle in liver were estimated. Dilution of 14C by 12C in the cycle was found in the fasted but not the fed state. In the fasted state, pyruvate carboxylation was estimated to be at least twice the rate of Krebs cycle flux and the rate of pyruvate's decarboxylation less than 1/25 the rate of its carboxylation. In the fed state, the rate of decarboxylation was estimated to be between one-sixth and one-half the rate of carboxylation. The rate of conversion of oxalacetate to fumarate in both states appeared to be greater than 6 times the rate of Krebs cycle flux.

Adult↗

PubMed1991

Metabolism of [2-14C]acetate and its use in assessing hepatic Krebs cycle activity and gluconeogenesis.

To examine the fate of the carbons of acetate and to evaluate the usefulness of labeled acetate in assessing intrahepatic metabolic processes during gluconeogenesis, [2-14C]acetate, [2-14C]ethanol, and [1-14C]ethanol were infused into normal subjects fasted 60 h and given phenyl acetate. Distributions of 14C in the carbons of blood glucose and glutamate from urinary phenylacetylglutamine were determined. With [2-14C]acetate and [2-14C]ethanol, carbon 1 of glucose had about twice as much 14C as carbon 3. Carbon 2 of glutamate had about twice as much 14C as carbon 1 and one-half to one-third as much as carbon 4. There was only a small amount in carbon 5. These distributions are incompatible with the metabolism of [2-14C]acetate being primarily in liver. Therefore, [2-14C]acetate cannot be used to study Krebs cycle metabolism in liver and in relationship to gluconeogenesis, as has been done. The distributions can be explained by: (a) fixation of 14CO2 from [2-14C]acetate in the formation of the 14C-labeled glucose and glutamate in liver and (b) the formation of 14C-labeled glutamate in a second site, proposed to be muscle. [1,3-14C]Acetone formation from the [2-14C]acetate does not contribute to the distributions, as evidenced by the absence of 14C in carbons 2-4 of glutamate after [1-14C]ethanol administration.

Acetates↗

PubMed1990

Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans.

The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway.

Adult↗

PubMed1990

Fructose-6-phosphate cycling and the pentose cycle in hyperthyroidism.

Hepatic fructose-6-phosphate (fructose-6-P) cycling and pentose cycle activity were quantified in hyperthyroid patients. A measure of the fructose-6-P cycle was the incorporation of 14C, on administering [3-3H,6-14C]galactose, into carbon 1 of blood glucose and the 3H/14C ratio in blood glucose. The measure of the pentose cycle was the randomization of 14C to carbon 1 of blood glucose on administering [2-14C]galactose. [2-3H]Galactose was also administered, so the 3H/14C ratio in blood glucose measured the extent of equilibration of glucose-6-P with fructose-6-P. Patients given [3-3H,6-14C]galactose were restudied when euthyroid. Of the 14C from [3-3H,6-14C]galactose, 7.7-9.5% was in carbon 1 of glucose in both states. 3H/14C ratios were also the same in both states. Fructose-6-P cycling was estimated to be 13 +/- 1% the rate of glucose turnover in the euthyroid and 15 +/- 1% that in the hyperthyroid state. The pentose cycle contributed about 2% to glucose utilization, similar to previous estimates in healthy humans. As in healthy individuals, about 25% of 3H was retained in the conversion of [2-3H]glucose-6-P to glucose. Thus, the fractions of glucose turnover participating in hepatic fructose-6-P and pentose cycling are similar in hyperthyroid and healthy subjects. As a result, augmented fructose-6-P cycling does not substantially contribute to increased hepatic oxygen consumption in hyperthyroidism.

Adult↗