Glucose Metabolism In Adipose Tissue Research Articles

Insulin, dexamethasone and their interactions in the control of glucose metabolism in adipose tissue from lactating and nonlactating sheep.

1. Lactation results in decreased glucose and acetate utilization and increased lactate output by sheep adipose tissue. 2. The ability of insulin to stimulate acetate uptake was lost in adipose tissue from lactating sheep, whereas both the response and the sensitivity (ED50) for insulin for stimulation of glucose conversion into products other than lactate were decreased. These impairments were partly restored by prolonged incubation of adipose tissue for 48 h. 3. The ability of insulin to stimulate lactate output was not altered by lactation. 4. Dexamethasone inhibited glucose uptake, lactate output and glycerol output in adipose tissue from both non-lactating and lactating sheep, with an ED50 of about 1 nM. Dexamethasone inhibited acetate uptake by adipose tissue from non-lactating sheep, but this effect was not observed with adipose tissue from lactating sheep. 5. Dexamethasone inhibited the stimulation of glucose uptake at all concentrations of insulin used; the effect varied with insulin concentration and resulted in an accentuation of the insulin dose-response curve. The insulin dose-response curve in the presence of dexamethasone was muted during lactation. 6. The overall effect of these adaptations is to ensure that glucose and acetate utilization by adipose tissue after an insulin surge is diminished during lactation.

Differences in glucose metabolic enzyme activities in human adipose tissue from abdominal and gluteal regions

In order to verify whether intersite differences exist in glucose metabolism of subcutaneous human adipose tissue, basal and insulin-stimulated 14C-1-glucose incorporation into triglycerides and the activities of some enzymes of glucose disposal were tested in abdominal and gluteal adipose tissue of 31 nondiabetic obese otherwise healthy women during isocaloric diet and after 2 weeks of very-low-calorie-protein-sparing modified diet. Basal 14C-1-glucose incorporation into triglycerides was quite similar in the adipose tissue of the two sites, and it was not influenced by dietary restriction. Insulin stimulated this metabolic activity to the same extent in both sites during isocaloric diet; after hypocaloric diet this effect of insulin was slightly decreased in adipose tissue of the abdominal site and completely abolished in the gluteal site. No enzymatic activity was different between the examined subcutaneous regions during the isocaloric diet; after very-low-calorie intake, hexokinase activity decreased in both sites, once again more markedly in the gluteal one; glucose-6-P-dehydrogenase activity decreased in the adipose tissue of the gluteal region only. These data suggest that glucose metabolism of the adipose tissue of the gluteal region is particularly decreased by severe calorie restriction. Therefore, since lipolysis does not occur at a higher rate in gluteal adipose tissue during calorie restriction, this tissue seems to undergo a resting metabolic phase during hypocaloric diet.

Chronic administration of theophylline to rats induces a post-insulin binding defect in adipocyte glucose transport.

To determine whether adenosine is involved in long-term regulation of glucose transport in adipose tissue, we have investigated effects of administration of an adenosine receptor antagonist (theophylline) on adipocyte glucose transport. Rats were injected with theophylline (30 mg/kg, dissolved in 0.9% NaCl) daily for 7 days. Controls were injected with saline. The rats were then killed, and epididymal adipocytes were isolated. Insulin-stimulated glucose transport rates were decreased by about 25%-30% in the cells from theophylline-treated rats at all insulin concentrations tested. The half-maximally effective concentration of insulin was not altered (6.5 +/- 0.5 and 6.7 +/- 0.5 mU/l in control and treated cells respectively), suggesting a post-insulin binding defect. This was confirmed by the finding that 125I-insulin binding to the cells was not altered. Adenosine receptor number and affinity (measured on detergent-solubilized adipocyte extracts using 125I-hydroxyphenylisopropyl adenosine) was also not changed by theophylline treatment. We conclude that theophylline administration causes decreased glucose transport rates in rat adipocytes at a post-insulin binding level. Thus, chronic adenosine receptor blockade impairs adipocyte glucose transport, suggesting that adenosine is involved in long-term regulation of glucose metabolism in adipose tissue.

Central endocrine regulation of the development of hormone responses in porcine fetal adipose tissue.

Experiments were performed to determine whether central endocrine or neural regulation is primarily involved with the development of endocrine responses in fetal adipose tissue metabolism. Fetuses within one uterine horn were either decapitated (decap) or spinally cauterized at 45 d of gestation, with fetuses in the other horn serving as sham controls (intact). Fetuses were removed by cesarean section at 110 d of gestation. Slices of subcutaneous adipose tissue (100 mg) were incubated in media supplemented with radioactive glucose and insulin (1.0 mU/ml) to measure the metabolic response of the tissue to insulin. Other slices were incubated in medium supplemented with norepinephrine bitartrate (1 microgram/ml) to measure lipolytic response by glycerol release. Basal glucose utilization for oxidation, total lipid and fatty acid synthesis was higher in decap adipose tissue than intact adipose tissue. Cauterized and intact fetuses did not differ in adipose tissue glucose metabolism. Only decap adipose tissue demonstrated an insulin stimulation of glucose oxidation and lipogenesis. Norepinephrine stimulated lipolysis in both cauterized and intact adipose tissue but had no effect upon decap adipose tissue lipolysis. These results demonstrate central endocrine regulation but not central neural regulation has an important function in the development of porcine fetal adipose tissue metabolism and its responses to systemic hormones.

Factors affecting measurements of glucose metabolism and lipolytic rates in porcine adipose tissue slices in vitro.

Porcine adipose tissue glucose metabolism and lipolytic rates have been measured for many years by numerous investigators. However, there is little or no documented indication of the effects of variation in tissue handling procedures or variations in incubation medium components on metabolic rates. We have systematically varied conditions to provide such documentation for these much used techniques. The temperature (18 to 38 C) of tissue during transport had little effect. The medium for tissue transport probably should be buffered. Use of Hepes buffer at greater than 10 or 25 mM in incubation media inhibited glucose metabolism and lipolysis. Calcium ion effects on glucose metabolism or lipolysis could not be demonstrated. Dimethyl sulfoxide should not be used routinely. Ascorbate at .56 mM did not inhibit glucose metabolism or lipolysis. Glucose metabolism was increased by glucose concentration to about 5 mM and not inhibited at higher concentrations; we recommend 10 or 20 mM glucose to ensure maximal rates. Insulin stimulated glucose metabolism but effects were slight, not related to insulin concentration and not consistently observed. Addition of some albumin preparations did not allow expression of insulin stimulation; we recommend albumin be omitted or, if included, carefully monitored. Lipolytic rates were dependent on albumin concentration, but rates were similar with all albumin preparations. Insulin markedly inhibited hormone-stimulated but not basal lipolysis. Adenosine, an inhibitor of lipolysis, did not affect glucose metabolism rates. An artificial oxygen carrier did not increase anabolic activity. Incubation in serum increased rates of glucose metabolism relative to lipolysis so that refinement of the incubation might lead to greater anabolic than catabolic rates in vitro to reflect the status of adipose tissue in growing pigs in vivo. Tissue handling and incubation conditions can markedly affect metabolic rates, and should be understood and controlled.

Postnatal expression of adipose tissue metabolic activity associated with a porcine genetic obesity.

To determine the age at which phenotypic expression of adipose tissue metabolic activities or adipocyte hypertrophy were detectable in a porcine obesity model, adipose tissue samples were obtained from genetically obese and lean pigs at 0, 7, 14, 21, 28, 42 and 56-d postpartum (weaning at 28 d). Adipocyte size was determined on osmium-fixed tissue slices using particle counter methods. Rates of glucose metabolism to CO2, total lipids and glyceride-fatty acids, as well as the basal and epinephrine plus theophylline-stimulated lipolytic rates were measured in tissue slices in vitro. Larger adipocytes were discernible in obese than lean pigs at birth and all subsequent postpartal ages. Expressed per cell, adipose tissue from obese pigs had greater glucose metabolism rates in vitro than that from lean pigs at 42 and 56 d; the rates were the same in obese and lean pigs at 28 d. Adipose tissue lipolytic rates in obese compared with lean pigs tended to be greater, were greater and were similar at 28, 42 and 56 d, respectively. These metabolic rates in vitro suggest that the early manifestation of the obesity evident as cell hypertrophy at birth and during early postnatal development is not the result of increased rates of adipose tissue glucose metabolism or decreased rates of adipose tissue lipid degradation.

Some Biochemical Effects of the Growth Hormone Analogue Produced by Plerocercoids of the Tapeworm Spirometra mansonoides on Carbohydrate Metabolism of Adipose Tissue from Normal, Diabetic, and Hypophysectomized Rats

Plerocercoids of Spirometra mansonoides produce a functional analogue of mammalian growth hormone (GH). Plerocercoid growth factor (PGF) mimics the growth-promoting actions of GH, but has not been shown to duplicate all of the actions reported for GH. The purpose of this study was to determine the effects of plerocercoid infection (chronic PGF treatment) on glucose metabolism of adipose tissue and to compare the effects to those elicited by insulin and GH in intact, diabetic, and hypophysectomized male rats. Groups of rats were constantly exposed to PGF (via plerocercoid infection) or injected twice daily with bovine GH, insulin, or saline for 10 days. Basal oxidation rates of [U-14C]glucose to 14CO2 in adipose tissue segments were measured in vitro immediately after tissue removal. Other aliquots of adipose tissue were preincubated in hormone-free medium for 3 hr prior to testing the ability of the tissue to respond to insulin or human GH (hGH) added in vitro. Adipose tissue from PGF-treated intact and hypophysectomized rats had significantly elevated basal glucose oxidation rates, and the tissue was sensitive to further stimulation by insulin or hGH. The results obtained with intact and hypophysectomized rats were essentially the same, indicating that the effects of PGF were not due to suppression of endogenous GH. The basal glucose oxidation rate in adipose tissue from diabetic rats was stimulated (P less than 0.01) by PGF, but the tissue was not sensitive to insulin added in vitro. Furthermore, PGF had no effect on body growth or blood glucose concentrations of diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose, acetate, and lactate metabolism in perirenal adipose tissue of fetal and newborn calves.

Rates of utilization of glucose, acetate, and lactate and activities of selected enzymes were determined in vitro to characterize the nature of lipogenesis and metabolite utilization in perirenal adipose tissue from 6- to 7-month old fetal and 3- to 4-h-old unsuckled newborn calves. Contribution of the pentose phosphate cycle to glucose metabolism was estimated using specifically labeled glucose. Rates of fatty acid synthesis from all three substrates and oxidation of glucose were much greater in fetal than in newborn adipose tissue. In fetal adipose tissue, acetate and lactate were major sources of carbon for fatty acid synthesis; glucose functioned mainly by metabolism via the pentose phosphate cycle to provide reducing equivalents for fatty acid synthesis and by incorporation into glyceride glycerol for fatty acid esterification. Pentose phosphate cycle contributed 58 and 12% to glucose metabolism in adipose tissue of fetal and newborn calves, respectively. Adipose tissue metabolism of newborn calves was characterized by greatly depressed rates of fatty acid synthesis despite high enzyme activities and elevated rates of glyceride glycerol synthesis.

Ability of growth hormone fragments to compete with 125I-iodinated human growth hormone for specific binding to isolated adipocytes of hypophysectomized rats

Several noncovalent complexes of large fragments of human GH, which are less active than native human GH in stimulating glucose metabolism in adipose tissue of hypophysectomized rats, were tested for their ability to compete with 125I-iodinated human GH for specific binding to isolated adipocytes of hypophysectomized rats. The complexes tested were A (residues 1–134 + residues 141–191; S-carbamidomethylated), B (residues 1–134 + residues 135–191; S-carbamidomethylated) and C (residues 1–134 + residues 135–191; S-carboxymethylated). When compared to native human GH, the complexes were less active in competing with 125I-iodinated human GH for specific binding to adipocytes, and their order of potency in the binding assay (A > B > C) was similar to that of their respective activities in stimulating glucose metabolism in isolated adipose tissue of hypophysectomized rats.

Metabolic effects of progesterone

Progesterone has important effects on carbohydrate, lipid and protein metabolism. This steroid induces hyperinsulinemia, possibly by direct action on pancreatic islets, while promoting glycogen storage in the liver. Paradoxically, it antagonizes the effects of insulin on glucose metabolism in adipose tissue and skeletal muscle. Progesterone stimulates deposition of body fat but had catabolic effects on protein metabolism. Provisional evidence is offered that the steroid may influence ketone body production by the liver as well. When these steroid actions are considered together, their most relevant expression appears to be the physiologic changes observed during normal pregnancy.

Physiological Effects of Caffeine in the Rat: Extracellular Cyclic AMP Status, Growth Pattern and Glucose Metabolism in Adipose Tissue

The authors investigated the effect of moderate caffeine intake on overall cyclic adenosine monophosphate (AMP) metabolism in the rat and its relationship to growth and glucose metabolism in adipose tissue. Male Sprague-Dawley weanling rats were divided into control and treatment groups. The latter received caffeine via drinking water (0.06 mg/ml H2O) during a 4-week period whereas controls received water only. At weekly intervals, urinary cyclic AMP excretion, food intake and weight gain were measured. Plasma cyclic AMP caffeine and glucose were determined at moment of death and in vitro lipogenesis and glycogen synthesis from [6-14C]glucose in epididymal adipose tissue were assayed. Although urinary cyclic AMP excretion was negatively correlated to caffeine intake during the 2nd week of the experiment, this did not reach significant levels, nor did this trend continue into the 4th week. Growth pattern and food efficiency were similar in both groups as were blood glucose and cyclic AMP values at moment of death. In vitro glycogen synthesis from [6-14C] glucose in adipose tissue showed a 40% increase, this parameter being positively correlated with plasma caffeine concentration. Glucose uptake and lipogenesis were unaltered in epididymal fat pads. These data suggest that regular intake of a moderate dose of caffeine leads to homeostasis of overall cyclic AMP metabolism and of selected physiological parameters under study. Alteration of glycogen synthesis in adipose tissue is discussed in relation to documented effects of caffeine ingestion on catecholamine secretion.caffeine extracellular cyclic AMP adipose tissue

Action of insulin on adipose tissue of diabetics

The insulin sensitivity of subcutaneous adipose tissue taken by biopsy from 11 healthy women and from 10 women with normal weight but recently diagnosed as suffering from diabetes mellitus was investigated. Unlike in the healthy subjects, no increase in the intensity of glucose oxidation to CO2 was produced in the adipose tissue of the diabetics by insulin in a concentration of 50 microunits/ml, and the synthesis of glycogen from glucose was not increased by insulin in concentrations of 50 and 100 microunits/ml. The decrease in the sensitivity of the various pathways of glucose metabolism in adipose tissue to insulin in diabetics points to the possibility of a disturbances of the interaction between insulin and the cell membrane in this disease.

Effects of hypophysectomy and acute growth hormone treatment upon glucose metabolism in adipose tissues and isolated adipocytes of rats.

Glucose oxidation and incorporation into lipid were measured in epididymal adipose tissues and isolated adipose cells of normal and hypophysectomized rats in an effort to determine whether the acute hypoglycemic effect of a systemic growth hormone (GH) injection was related to alterations in the glucose metabolism of adipose tissue. The rats were fed rat chow or a high sucrose diet and received 100 mug GH intraperitoneally 30 minutes or three and one-half hours before sacrifice. Hypophysectomized rats showed a lower plasma glucose as compared with normal rats on both diets. Thirty minutes after a GH injection there was a further decrease of the plasma glucose which, however, was not present in those rats receiving GH three and one-half hours before sacrifice. Adipose tissues from hypophysectomized rats fed the high sucrose diet showed a blunted insulin sensitivity as compared with normal rats on a similar diet. The insulin sensitivity of these tissues was further decreased 30 minutes after a GH injection. Basal glucose metabolism of isolated adipocytes from hypophysectomized rats, as compared with normal rats, was depressed if they were fed rat chow, was at normal levels if they were fed the high sucrose diet and was increased if they were fed the sucrose diet and received triiodothyronine and cortisone supplements. No manipulations of diet or hormonal treatments made the isolated adipocyte from hypophysectomized rats sensitive to insulin either 30 minutes or three and one-half hours after a GH injection. Since basal glucose utilization is not enhanced by GH injection and both the blunted insulin sensitivity of adipose tissue and the absent insulin sensitivity of adipopocytes would be expected to produce hyperglycemia rather than hypoglycemia, it is concluded that immediate systemic effects of a GH injection on carbohydrate metabolism are not related to changes in glucose metabolism of the peripheral adipose tissues.

The physiological significance of the xanthurenic acid-insulin comples.

The xanthurenic acid-insulin complex was found to have similar immunological properties to native Zn-insulin. This complex showed less hormonal activity on glucose metabolism in adipose tissue than native An-insulin, but its activity was increased by addition of Zn2+ ions.

Adipose Tissue Metabolism in Essential Fatty Acid Deficiency

In an effort to better define some of the metabolic changes that accompany essential fatty acid deficiency (EFAD), we studied glucose metabolism in adipose tissue of EFAD and normal mice under basal conditions and in the presence of prostaglandin E1 (PGE1), epinephrine, and ACTH1-18. Isolated fat cells were incubated in Krebs-Ringer bicarbonate medium containing glucose 1(-14C) or 6(-14C), and the incorporation of radioactive carbon into CO2, total fat, fatty acids, and glyceride-glycerol was determined. It was found that EFAD increased glucose uptake over controls which could be attributed to increased oxidation to CO2 and fatty acid synthesis. The contribution of the pentose cycle to glucose oxidation was 50-80% higher in EFAD adipocytes as compared to controls. ACTH1-18 (0.1 mug/ml) suppressed this by 18 and 30% in the control and EFAD groups, respectively, while epinephrine decreased pentose cycle activity by 83 and 55% in the two groups, respectively. PGE1 alone had no significant effect, but in combination with epinephrine it abolished the inhibitory action of the catecholamine in both groups. It is suggested that, although EFA serve as prostaglandin precursors, the effects of EFAD on the metabolism of fat cells cannot be reversed by PGE1, in vitro. However, these fat cells retain their responsiveness to the action of both lipolytic (ACTH and epinephrine) and antilipolytic (PGE1) agents.

Paradoxical effects of theophylline and its interaction with insulin on glucose metabolism in adipose tissue.

The effects of theophylline on the metabolism of glucose by rat epididymal adipose tissue from fed and fasted rats were studied. The addition of 0.5 mg theophylline per ml to the incubation medium caused a large decrease in the conversion of medium glucose to fatty acids, glyceride glycerol, and CO2 and a large increase in lipolysis in tissue from both fed and fasted rats. This increase in lipolysis was not blocked by large concentrations of insulin even though insulin was able to overcome the inhibition of glucose metabolism. When tissue from fed rats was incubated 1 h with theophylline, rinsed, and then incubated 2 h without theophylline, the glucose uptake during the latter period was increased. Glucose oxidation to CO2, conversion to fatty acids and to glyceride glycerol were all enhanced. This paradoxical “preincubation effect” did not appear when tissue from fasted rats was studied. The possible role of cyclic AMP in regulating the utilization of glucose is discussed.

Similar and opposite effects of dibutyryl cyclic AMP and insulin on glucose metabolism in adipose tissue.

Abstract The effects of N6-2′-O-dibutyryl cyclic AMP on glucose metabolism and lipolysis in fragments of rat epididymal adipose tissue were studied. Measurements were made of glucose uptake, conversion of glucose carbon to CO2 and tissue fatty acids and glyceride-glycerol, lactate production, and glycerol release. Low concentrations of dibutyryl cyclic AMP (0.1–0.5 mM) increased all parameters of glucose metabolism and inhibited glycerol release in tissue from both normally fed and fasted rats. Higher concentrations of dibutyryl cyclic AMP (3–5 mM) diminished glucose utilization and greatly accelerated lipolysis. Insulin, 50 μunits/ml, accelerated glucose metabolism in the presence of either low or high concentrations of dibutyryl cyclic AMP though the effect of insulin was greatly reduced by 3 mM dibutyryl cyclic AMP. Tissue exposed to concentrations of dibutyryl cyclic AMP which inhibited glucose metabolism (5 mM), then rinsed and reincubated without dibutyryl cyclic AMP, displayed increased glucose utilization. The results of these experiments emphasize the need for caution in interpretation of the effects of dibutyryl cyclic AMP on adipose tissue metabolism and the need for further research to elucidate the role of cyclic AMP in the regulation of glucose metabolism.

Growth hormone-induced enhancement of insulin sensitivity in adipose tissue.

In vitro basal and insulin stimulated glucose metabolism (I4CO2 production and 14C glucose incorporation into fatty acids) are enhanced in the epididymal fat pads of fed Sprague Dawley rats exposed to intraperitoneal growth hormone (GH) both acutely (90 minutes after a single 1 mg injection) and chronically (24 hours after the last of a 15 day series of 1 mg GH injections). This enhancement of the glucose metabolism in the fat pad is accompanied by depletion of its lipid content. This alteration in glucose metabolism in adipose tissue exposed to GH in vivo may be related to the action of GH in accelerating intracellular free fatty acid turnover and/or may be subsequent to a decrease in the size of the fat cell.

Physiologic and genetic influences on regulation of glucose metabolism in adipose tissue of mice.

The influence of various agouti locus genotypes and phenotypes, castration, fat content of the diet and their interactions on the rates of glucose oxidation and conversion to lipid, blood glucose level, epididymal adipose tissue weight and body weight has been studied in male mice of the inbred YS/ChWf, VY/Wf, C3H/DiHeWf-Avy and NZO/BlWf strains. Although the lethal yellow (Ay) and viable yellow (Avy) genes, castration and a high fat content diet, all increased epididymal adipose tissue weight, the inducing mechanisms are probably different for each of these factors.

Lipogenic activity of a potent lipolytic hormone: sheep beta lipotropin (beta-LPH). A comparative study of the effects of beta-LPH and insulin on in vitro glucose metabolism of adipose tissue.

Lipogenic activity of a potent lipolytic hormone: sheep beta lipotropin (beta-LPH). A comparative study of the effects of beta-LPH and insulin on in vitro glucose metabolism of adipose tissue.