Metabolic patterns and insulin responsiveness of enlarging fat cells

The rate and pattern of glucose metabolism, basal lipolysis, and intracellular concentration of free fatty acids were determined in isolated epididymal fat cell preparations (mean volume 30-800 pl) from rats on the basis of fat cell number and in relation to the cell volume. The effects of increasing glucose concentrations in the medium and of insulin on the cellular metabolic activities were compared. Expanding fat cell volume correlated positively and significantly (P < 0.001) with the synthesis of glyceride glycerol from glucose (correlation coefficient, r = 0.919), with rates of basal lipolysis (r = 0.663), and with intracellular free fatty acid accumulation (r = 0.796); it correlated negatively and significantly with glucose conversion to glyceride fatty acids (r = -0.814, P < 0.01). The differences in patterns of glucose metabolism and basal lipolysis between small (<100 pl) and large (>400 pl) fat cells were not modified by insulin or by increments in glucose concentration. The results indicate that the reduced capacity of the large fat cells to respond to insulin cannot be attributed solely to a limited capacity of the cells to take up and metabolize increasing amounts of glucose. The acquired unresponsiveness of the large cells to insulin may result from an alteration in the mechanism of action of insulin and may be related to an intracellular metabolic derangement with increased basal lipolysis, free fatty acid accumulation, and accelerated glyceride synthesis resulting from the accumulation of triglyceride.     

Effects of cell size and animal age on glucose metabolism in pig adipose tissue

Adipose tissue slices were prepared from middle subcutaneous or perirenal adipose tissue excised from pigs of different ages (and obesity) and incubated with [U-14C]glucose. After incubation, the slices were fixed with osmium tetroxide and separated into diameter ranges of 20--63, 63--102, and 102--153 microgram, respectively. Following determination of cell size and number, the fixed adipocytes were decolorized with H2O2 prior to quantification of glucose conversion to total lipid, glyceride fatty acids, glycerideglycerol, and CO2. Glucose conversion to total lipid or CO2 was unaffected by the presence of purified porcine insulin (0, 10, 100, 1000, and 100,000 microM/ml). Within animals, adipocytes of different sizes were not different with regard to insulin sensitivity. Within a weight (age) group, conversion of glucose to total lipid (insulin present) or to glyceride fatty acids and glyceride-glycerol (insulin absent) per cell was significantly greater in large adipocytes compared to small adipocytes, regardless of the group examined. With increasing weight or age, there was a markedly decreased conversion of glucose to total lipid and glyceride fatty acids among adipocytes of similar size within a cell-size fraction. The diminution in glucose metabolism was greater (as a percentage) in 20--63 microgram adipocytes than for 63--102 or 102--153 microgram adipocytes. However, for all cell-size fractions there was a marked decrease in glucose conversion to fatty acids. Glyceride-glycerol synthesis was impaired in adipocytes from older pigs, but the decrease was less than observed for glyceride fatty acid synthesis.     

Some aspects of metabolic adaptations in lipid metabolism during starvation are mimicked by epinephrine in rat adipocytes

1. The effects of fasting on the neutral lipid synthesis to insulin and/or epinephrine in isolated fat cells have been examined using [1-14C]glucose. 2. The ability of adipocytes from starved rats to synthesize fatty acids from both labeled substrates was markedly diminished compared to adipocytes from control rats. 3. The response of lipogenic stimulation to insulin at all concentrations tested was greatly diminished in adipocytes from 24 hr starved rats. 4. [1-14C]glucose utilization rates in the absence or in the presence of insulin were not significantly different in adipocytes from 24 hr starved rats as compared with control adipocytes, although basal and insulin stimulated glyceride-glycerol synthesis were significantly higher in starved adipocytes. 5. Epinephrine acutely inhibited [1-14C]acetate incorporation into fatty acids for insulin-stimulated lipogenesis in control adipocytes, in contrast, this lipolytic agent strongly increased [1-14C]glucose conversion to triacylglycerols. 6. In both cases, the differences in lipid synthesis capacities found in both nutritional states were abolished by epinephrine.     

Very small fat cells. II. Initial observations on basal and hormone-stimulated metabolism

Very small fat cells (less than 35 micron diameter) and normal large fat cells (greater than 40 micron diameter) were isolated from adult Fischer 344 rat epididymal adipose depots. These very small fat cell preparations were free from normal, large fat cells (40-130 micron diameter) and stromal-vascular elements. Examination by electron microscopy and lipid analysis showed a similarity in overall organization and composition to normal, large fat cells. Incubations with [U-14C]glucose showed that the very small fat cell preparations oxidized glucose in proportion to both cell number and time. These preparations also responded to insulin, increasing [U-14C]glucose oxidation in a manner similar to normal large fat cell preparations (i.e., 2- to 4-fold increases in CO2 production with insulin stimulation). The very small fat cells also incorporated radiolabeled glucose into lipids; but, unlike normal large fat cells, insulin failed to stimulate this process. Glycerol release from very small fat cells was stimulated by lipolytic hormones in a manner similar to these responses in co-isolated large fat cells.     

Endurance training and glucose conversion into triglycerides in human fat cells

To study the influence of endurance training on glucose conversion into fat cell triglycerides, 24 (13 women, 11 men) inactive subjects (25.0 +/- 3.8 yr of age) took part in a 20-wk ergocycle training program 4 days and increasing to 5 days/wk, 40-45 min/day, starting at 60% and increasing to 85% of the heart rate reserve. Several body fatness indicators were measured before and after the training program: seven skinfold thicknesses, percent fat, and mean fat cell weight. Fat cell basal and maximal insulin-stimulated glucose conversion into triglycerides were also determined using [14C]glucose. Body fatness indicators decreased significantly after training only in male subjects (P less than 0.05). Basal and maximal insulin-stimulated glucose conversion into triglycerides increased significantly with training (P less than 0.05): pretest values (nanomoles glucose per hour per 10(6) cells) being 24.9 +/- 2.1 and 28.7 +/- 2.5, while post-test values were 30.1 +/- 3.2 and 33.0 +/- 3.4 for basal and insulin-stimulated values, respectively. However, this lipogenic increase was only observed in male subjects (P less than 0.01). Changes in body fatness indicators induced by training were negatively correlated with changes induced in fat cell glucose conversion into triglycerides (-0.24 less than or equal to r less than or equal to -0.45). These results demonstrate that endurance training increases fat cell glucose conversion into triglycerides and suggest that adipose tissue metabolism is part of the adaptive response to training. Moreover, it appears that adipose tissue response to aerobic training is more efficient in males than in females.     

Effects of prolonged incubation and cell concentration on lipogenesis from glucose in isolated human omental fat cells

The behavior of human omental fat cells in vitro has been examined in order to define conditions under which glucose is converted to glyceride-glycerol and glyceride fatty acids. Synthesis of glyceride fatty acids from glucose reached maximal rates only after several hours of incubation in Krebs-Henseleit bicarbonate buffer, with or without added bovine albumin. Conversion of glucose to glyceride fatty acids was readily demonstrable with concentrated cell suspensions and was stimulated 3- to 8-fold by insulin. With dilute cell suspensions, little fatty acid was synthesized even after prolonged incubation in the presence of insulin. Conversion of glucose to glyceride-glycerol was linear during 6-hr incubations in buffer and unaffected by the concentration of the cell suspension. In the presence of bovine albumin, glyceride-glycerol synthesis was readily demonstrable at all cell concentrations used, although synthesis was faster in dilute suspensions. Thus, different incubation conditions produce widely divergent patterns of glucose metabolism in human omental fat cells.     

Enhanced utilization of glycerol for glyceride synthesis in isolated adipocytes from early pregnant rats

Adipose tissue normally has low glycerol kinase activity, but its expression is enhanced under conditions of augmented insulin sensitivity and/or obesity. Since these conditions occur during early pregnancy, the comparative utilization of glucose or glycerol by isolated adipocytes from rats at 0, 7, 14, or 20 days of pregnancy was studied. Incubations were carried out in the presence of [U¹⁴C]-glucose or -glycerol in medium supplemented or not with 5 mM glucose and 100 nM insulin. The conversion of glucose into esterified fatty acids and glyceride glycerol was greatest in adipocytes from 7-day pregnant rats, the effect being further enhanced by insulin. Both the amount of aquoporin 7 and the in vitro conversion of glycerol into glyceride glycerol were greatest in adipocytes of 7-day pregnant rats, the later being unaltered by insulin. In the presence of glucose, the overall glycerol utilization was lower than in its absence and glycerol conversion into glyceride glycerol was further decreased by insulin, the effect only being significant in adipocytes from 7-day pregnant rats. It is proposed that the enhanced utilization of glycerol for glyceride glycerol synthesis in adipose tissue contributes to the net accumulation of fat depots that normally takes place in early pregnancy.     

Effect of sparteine sulfate on insulin secretion in normal men

This study aimed at evaluating the influence of sparteine sulfate either upon basal plasma glucose and insulin or glucose-induced insulin secretion in normal man. Thirteen overnight fasted volunteers took part in this study; five of them were submitted to sparteine sulfate bolus (15 mg in 10 ml of saline solution) followed by a slow infusion (90 mg/100 ml X 60 min) and eight subjects underwent two different glucose pulses (20 gr. i.v.) in absence or in presence of sparteine, infused as described above. In basal conditions, along with sparteine infusion, plasma glucose showed a progressive and significant decrease (P less than 0.0001) and plasma insulin was significantly higher from min 10 to 120' (P less than 0.0005-0.001). Even during the glucose-induced insulin secretion, in the presence of sparteine infusion, plasma glucose levels were significantly lower while plasma insulin levels were significantly higher when compared to those observed after glucose alone. The acute insulin response (AIR) was 42 +/- 10 microU/ml after glucose alone vs 67 +/- 9 microU/ml after glucose plus sparteine (P less than 0.05). Total insulinemic areas were significantly different being 1410 +/- 190 vs 2250 +/- 310 microU/ml/min (P less than 0.001) during glucose and glucose plus sparteine infusion, respectively. This study thereby, demonstrates that in normal man sparteine sulfate, administrated by intravenous infusion, is able to increase either basal or glucose-induced insulin secretion.     

Effects of age and cell size on rat adipose tissue metabolism.

In order to analyze separately the effects of cell size and age on the metabolism of rat adipose tissue, fat cells of different sizes were obtained from the same animals. The rats were 4 or 15 wk old. The results show that age as well as cell size influences the metabolic rates. At a given cell size, the basal lipolysis, the lipolytic effects of glucagon and noradrenaline, the rate of glucose incorporation into the triglycerides, and the effect of insulin on glucose metabolism were considerably increased in the young animals. Furthermore, irrespective of fat cell size the lipolytic action of glucagon was reduced in old animals. The data thus show that experiments with large fat cells from old rats and with small cells from young animals cannot be directly compared because both variables may influence metabolic reactions.     

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psoas muscle attenuation measurement with computed tomography indicates intramuscular fat accumulation in patients with the HIV-lipodystrophy syndrome.

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is characterized by abnormalities of lipid metabolism, glucose homeostasis, and fat distribution. Overaccumulation of intramuscular lipid may contribute to insulin resistance in this population. We examined 63 men: HIV positive with lipodystrophy (n = 22), HIV positive without lipodystrophy (n = 20), and age- and body mass index-matched HIV-negative controls (n = 21). Single-slice computed tomography was used to determine psoas muscle attenuation and visceral fat area. Plasma free fatty acids (FFA), lipid profile, and markers of glucose homeostasis were measured. Muscle attenuation was significantly decreased in subjects with lipodystrophy [median (interquartile range), 55.0 (51.0-58.3)] compared with subjects without lipodystrophy [57.0 (55.0-59.0); P = 0.05] and HIV-negative controls [59.5 (57.3-64.8); P < 0.01]. Among HIV-infected subjects, muscle attenuation correlated significantly with FFA (r = -0.38; P = 0.02), visceral fat (r = -0.49; P = 0.002), glucose (r = -0.38; P = 0.02) and insulin (r = -0.60; P = 0.0001) response to a 75-g oral glucose tolerance test. In forward stepwise regression analysis with psoas attenuation as the dependent variable, visceral fat (P = 0.02) and FFA (P < 0.05), but neither body mass index, subcutaneous fat, nor antiretroviral use, were strong independent predictors of muscle attenuation (r2 = 0.39 for model). Muscle attenuation (P = 0.02) and visceral fat (P = 0.02), but not BMI, subcutaneous fat, FFA, or antiretroviral use, were strong independent predictors of insulin response (area under the curve) to glucose challenge (r2 = 0.47 for model). These data demonstrate that decreased psoas muscle attenuation due to intramuscular fat accumulation may contribute significantly to hyperinsulinemia and insulin resistance in HIV-lipodystrophy patients. Further studies are needed to assess the mechanisms and consequences of intramuscular lipid accumulation in HIV-infected patients.     

Measurement of flow of carbon atoms from glucose and glycogen glucose to glyceride glycerol and glycerol in rat heart and epididymal adipose tissue: Effects of insulin, adrenaline and alloxan-diabetes

1. Flow of carbon atoms from glucose and glycogen glucose to glyceride glycerol, glyceride fatty acids and glycerol was calculated in the perfused rat heart and incubated epididymal adipose tissue from the incorporation of (14)C from [U-(14)C]-glucose (into glyceride glycerol, glyceride fatty acids and glycerol in the medium), and from measurements of the specific activity of l-glycerol 3-phosphate, and the effects of insulin, adrenaline and alloxan-diabetes were studied. Measurements were also made of the uptake of glucose and the outputs of lactate, pyruvate and glycerol. 2. New methods are described for the measurement of radioactivity in small amounts of metabolites (glycerol, glucose 6-phosphate and fructose 6-phosphate and l-glycerol 3-phosphate) in which use has been made of alterations in charge induced by enzymic conversions to effect resolution by ion-exchange chromatography. 3. In hearts the specific activity of l-glycerol 3-phosphate was less than that of glucose in the medium but similar to that of lactate released during perfusion. Because repeated measurements of the specific activity of l-glycerol 3-phosphate was impracticable, the specific activity of lactate has been used as an indirect measurement of glycerol phosphate specific activity. 4. In fat pads, specific activity of lactate was the same as that of glucose in the medium and thus the specific activity of l-glycerol 3-phosphate was taken to be the same as that of medium glucose. 5. In hearts from alloxan-diabetic rats, despite decreased glucose uptake and l-glycerol 3-phosphate concentration, flow of carbon atoms through l-glycerol 3-phosphate to glyceride glycerol was increased about threefold. 6. In fat pads, flow of carbon atoms through l-glycerol 3-phosphate to glyceride glycerol was increased by insulin (twofold), by adrenaline in the presence of insulin (fivefold) and by diabetes in pads incubated with insulin (1.5-fold). These increases could not be correlated either with increases in glucose uptake, which was unchanged by adrenaline and decreased in diabetes, or with the concentration of l-glycerol 3-phosphate, which was decreased by adrenaline and unchanged in diabetes. 7. These results are discussed in relation to the control of glyceride synthesis in heart and adipose tissue and to the regulation of glyceride fatty acid oxidation in the perfused rat heart.     

Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0-33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat (r = 0.82, P < 0.001) and liver fat (r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal (r = 0.60, P = 0.008), intra-abdominal (r = 0.75, P = 0.0001) and liver (r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal (r = -0.72, P = 0.001) and intra-abdominal (r = -0.55, P = 0.015) but not liver (r = -0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.     

Insulin secretion and action in the hyperthyroid rat

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.     

The regulation of glyceride synthesis in isolated white-fat cells. The effects of palmitate and lipolytic agents

1. 0.5mm-Palmitate stimulated incorporation of [U-¹⁴C]glucose into glyceride glycerol and fatty acids in normal fat cells in a manner dependent upon the glucose concentration. 2. In the presence of insulin the incorporation of 5mm-glucose into glyceride fatty acids was increased by concentrations of palmitate, adrenaline and 6-N-2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate up to 0.5mm, 0.5μm and 0.5mm respectively. Higher concentrations of these agents produced progressive decreases in the rate of glucose incorporation into fatty acids. 3. The effects of palmitate and lipolytic agents upon the measured parameters of glucose utilization were similar, suggesting that the effects of lipolytic agents are mediated through increased concentrations of free fatty acids. 4. In fat cells from 24h-starved rats, maximal stimulation of glucose incorporation into fatty acids was achieved with 0.25mm-palmitate. Higher concentrations of palmitate were inhibitory. In fat cells from 72h-starved rats, palmitate only stimulated glucose incorporation into fatty acids at high concentrations of palmitate (1mm and above). 5. The ability of fat cells to incorporate glucose into glyceride glycerol in the presence of palmitate decreased with increasing periods of starvation. 6. It is suggested that low concentrations of free fatty acids stimulate fatty acid synthesis from glucose by increasing the utilization of ATP and cytoplasmic NADH for esterification of these free fatty acids. When esterification of free fatty acids does not keep pace with their provision, inhibition of fatty acid synthesis occurs. Provision of free fatty acids far in excess of the esterification capacity of the cells leads to uncoupling of oxidative phosphorylation and a secondary stimulation of fatty acid synthesis from glucose.     

Apparent translocation of glucose transport activity in rat epididymal adipocytes by insulin-like effects of high pH or hyperosmolarity

The basal and plus insulin states of glucose transport activity in adipocytes are known to show different responses to changes in the pH or osmolarity of the incubation mixture. When the pH was raised from 7 to 8, the basal glucose transport activity (assessed from the rate of 3-O-methyl-D-glucose uptake) was increased approximately 3-fold while the plus insulin activity remained virtually unaffected. Likewise, when cells were exposed to 300 mM sorbitol, the basal glucose transport activity, but not the plus insulin activity, was considerably increased. In both cases, the change in the transport activity was ATP-dependent and was completed in approximately 60 min. The increase in the cellular glucose transport activity was accompanied, in both cases, by an increase in the glucose transport activity in the plasma membrane fraction and a decrease in the activity in the high-speed pellet fraction. The transport activity in the subcellular fractions was determined after reconstitution into egg lecithin liposomes. Both isotonic buffer at pH 8.0 and hypertonic buffer at pH 7.4 significantly stimulated membrane-bound cAMP phosphodiesterase in adipocytes. It is concluded that the above two experimental conditions may induce insulin-like effects in fat cells and may facilitate translocation of the glucose transport activity from an intracellular site to the plasma membrane.     

Glucose metabolism in isolated fat cells: enhanced response of larger adipocytes from older rats to epinephrine and adrenocorticotropin.

The effects of insulin and of two lipolytic hormones (epinephrine and ACTH1) on the rate and pattern of glucose metabolism were compared during incubation of isolated fat cells, obtained from epididymal fat pads of rats of varying age and degrees of adiposity. Glucose metabolism and the intracellular free fatty acid levels were expressed on a per cell basis and in relation to adipocyte size. The data for total glucose metabolism show that, in contrast to the declining insulin effect observed with adipocyte enlargement, the stimulation of glucose uptake and metabolism by these lipolytic hormones was significantly greater in the larger fat cells from the older fatter rats than in the smaller ones from the younger leaner rats. Lipolytic hormones suppressed, whereas insulin enhanced, fatty acid synthesis; moreover the lipolytic hormones stiumlated glucose ce effect of epinephrine on the intracellular free fatty acid levels was greater in the small fat cells than in the large ones; this effect of epinephrine was markedly curtained by the presence of glucose in the incubation medium, making it unlikely that acceleration of glucose metabolism by the lipolytic stimulus was mediated by an elevation of the intracellular free fatty acid level. The present results show a markedly enhanced capacity of the large adipocytes to accelerate glucose metabolism in response to these liplytic hormones. Thus, in contrast to prevailing notions of declining hormonal responsiveness with expanding fat cell size in older and more obese animals, this study documents an instance of increased hormonal response in enlarged adipocytes and points to the need for a more comprehensive reevaluation of the various hormonal effects in adipocytes of different size.     

Immunoreactive insulin and obesity in women.

The authors investigated basal and glucose stimulated (50 g by mouth) IRI values in women with normal weight and obese women (58) under conditions of balanced body-weight and after its reduction. The body composition was determined (from body density), and from specimens of subcutaneous abdominal adipose tissue also the size of fat cells and their total number. In obese women significantly higher IRI levels (basal and stimulated) were found as compared with controls and these values had a marked tendency towards normalization after reduction of body weight. The authors found significant relations between IRI values and the degree of obesity, fat content and lean body mass. The closest correlation was found between the stimulated IRI values and Broca's index (r = +0.8227). Between the loss of body-weight and body fat and between changes of IRI in obese subjects no significant relations were found. Investigation of the relationship of IRI and the size and total number of fat cells revealed marked associations between basal values and the sum of stimulated IRI values and the size of the fat cell. Relations between IRI and the total number of fat cells were not significant. When investigating the relationship between the incidence of obesity in the family and IRI values it was revealed that the group of obese women with obese mothers, as compared with the group who had neither parent obese, had a significantly higher basal IRI value and IRI value after stimulation with glucose during the 120th and 180th minute, the higher basal value in the group with an obese father was not significant. After weight reduction the differences between basal and stimulated IRI values were not significant.     

Effect of insulin on glucose uptake in near-term fetal lambs

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.     

Effect of epinephrine on the synthesis of glyceride glycerol in adipose tissue in vitro.

In order to study the effect of epinephrine on the rate of esterification of fatty acids in adipose tissue, pieces of epididymal fat pad were incubated in KRB in the presence of purified albumin, glucose and either 1-14C-glycerol, 1-14C-glucose or 6-14C-glucose. Epinephrine enhances the production of glycerol but reduces the uptake of 1-14C-glycerol by the tissue and its conversion to 14CO2, 14C-fatty acids and 14C-glyceride glycerol. When the change in specific activity of the tracer is taken into account the effect of epinephrine on the utilization of glycerol by the tissue is only observed in the reduction of glyceride glycerol synthesis. When 14C-labelled glucose was used as tracer, epinephrine enhances both the production of 14CO2 from 6-14C-glucose and the synthesis of 14C-glyceride glycerol from 1-14C and 6-14C-glucose. The contrasting effects of epinephrine on the glyceride glycerol formation from glycerol and from glucose can explain the difficulties found in observing any change in the net rate of esterification of fatty acids by adipose tissue.