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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activities in rat tissues of 3-oxo acid CoA-transferase (the first enzyme involved in acetoacetate utilization) were found to be highest in kidney and heart. In submaxillary and adrenal glands the activities were about one-quarter of those in kidney and heart. In brain it was about one-tenth and was less in lung, spleen, skeletal muscle and epididymal fat. No activity was detectable in liver. 2. The activities of acetoacetyl-CoA thiolase were found roughly to parallel those of the transferase except for liver and adrenal glands. The high activity in the latter two tissues may be explained by additional roles of thiolase, namely, the production of acetyl-CoA from fatty acids. 3. The activities of the two enzymes in tissues of mouse, gerbil, golden hamster, guinea pig and sheep were similar to those of rat tissues. The notable exception was the low activity of the transferase and thiolase in sheep heart and brain. 4. The activities of the transferase in rat tissues did not change appreciably in starvation, alloxan-diabetes or on fat-feeding, where the rates of ketone-body utilization are increased. Thiolase activity increased in kidney and heart on fat-feeding. 5. The activity of 3-hydroxybutyrate dehydrogenase did not change in rat brain during starvation. 6. The factors controlling the rate of ketone-body utilization are discussed. It is concluded that the activities of the relevant enzymes in the adult rat do not control the variations in the rate of ketone-body utilization that occur in starvation or alloxan-diabetes. The controlling factor in these situations is the concentration of the ketone bodies in plasma and tissues.
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PMID:Activities of enzymes involved in acetoacetate utilization in adult mammalian tissues. 516 21

1. Methods are described for the extraction and assay of ATP, ADP, AMP, glucose 6-phosphate, l-glycerol 3-phosphate and citrate in rat epididymal adipose tissue incubated in vitro for 1hr. At this time of incubation rates of glucose uptake and outputs of glycerol, free fatty acids, lactate and pyruvate were shown to be constant. 2. In fat pads incubated in medium containing glucose (3mg./ml.) and albumin (20mg./ml.) the concentrations (in mmumoles/g. wet wt.) were: ATP, 70; ADP, 36; AMP, 9.0; glucose 6-phosphate, 3.0; l-glycerol 3-phosphate, 3.3; citrate, 8.1. 3. The volume of intracellular water calculated from ([(3)H]water space-[(14)C]sorbitol space), ([(14)C]urea space-inulin space) and (weight loss on drying-[(14)C]sorbitol space) was 1.4ml./100g. wet wt. of tissue. The intracellular volume was not changed by insulin, alloxan-diabetes or adrenaline. 4. When compared in terms of mumoles/ml. of intracellular water the concentration of ATP in adipose tissue was less than in heart and diaphragm muscles. The concentrations of ADP and AMP were greater both in absolute terms and relative to ATP. Insulin, alloxan-diabetes and adrenaline had no significant effects on the concentrations of the adenine nucleotides in adipose tissue. 5. The concentration of glucose 6-phosphate was increased by insulin and lowered by alloxan-diabetes and adrenaline. The concentration of l-glycerol 3-phosphate was increased by insulin, unchanged by alloxan-diabetes and lowered by adrenaline. The concentration of citrate was increased by adrenaline and alloxan-diabetes and unchanged by insulin. 6. The effect of glucose concentration in the medium on rates of glucose uptake in adipose tissue from normal rats and alloxan-diabetic rats was investigated. The K(u) of glucose uptake was 29-44mg./100ml. and the V(max.) was 0.77mg./g. wet wt. of tissue/hr. Insulin increased the V(max.) and alloxan-diabetes diminished it, but neither agent significantly altered the K(u). 7. The significance of these results in relation to control of metabolism of adipose tissue is discussed.
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PMID:Measurement of concentrations of metabolites in adipose tissue and effects of insulin, alloxan-diabetes and adrenaline. 596 39

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.
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PMID: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. 604 84

The effect of constant, controlled hyperinsulinemia on in vivo and in vitro insulin responsiveness has been investigated in rats that have received insulin infusions through chronically implanted jugular vein catheters. Constant rates of insulin infusion during days 1-4 resulted in stable plasma insulin concentrations. The plasma glucose initially fell from 122 +/- 3 to 53 +/- 4 mg/dl. While the infusion rate was maintained constant, the plasma glucose continued to fall over the subsequent days so that on day 4 the plasma glucose, 40 +/- 2 mg/dl, was significantly lower than that in the same animals on day 1 (P less than 0.02). Subsequently, the rate of insulin infusion was decreased to maintain the plasma glucose level in the 35-40 mg/dl range. Plasma catecholamine levels were high in insulin-infused rats. On the eighth day an in vivo insulin tolerance test (0.5 U/kg) was performed. Insulin-infused rats responded with a hypoglycemia that was both more pronounced and longer sustained than in saline-infused controls. Insulin responsiveness in vitro has been measured in isolated adipocytes. Adipocytes from epididymal fat pads were of similar size in the two groups of animals. Glucose uptake by adipocytes from insulin-infused rats was similar to that of controls under basal (zero insulin) conditions, but showed an increase in the maximum response to insulin. Glucose incorporation into total lipid and fatty acid was greater in adipocytes from insulin-infused rats than in controls under both basal (zero insulin) and insulin-stimulated conditions. Activities of the lipogenic enzymes acetyl CoA carboxylase and fatty acid synthetase were markedly increased in epididymal fat pads of insulin-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 May
PMID:Increased insulin responsiveness in vivo and in vitro consequent to induced hyperinsulinemia in the rat. 614 6

It is well documented that long-term diabetes mellitus results in numerous deleterious consequences. However, considerable controversy exists concerning male reproductive function in diabetes. The purpose of this investigation was to study several endocrine parameters in diabetic male rats with emphasis on Sertoli cell function. Male Wistar rats were injected with streptozotocin and then either left untreated for 30 days or injected with insulin so as to prevent spillover of glucose into the urine. These two groups were compared with control animals that had only been injected with the vehicle for streptozotocin. Semi-starved control animals were included to determine if any of the potential endocrine alterations were related to body weight changes which occur in streptozotocin-injected rats. It was found that FSH, LH, PRL, and GH serum levels were reduced in diabetic animals. Only FSH was restored to normal by insulin injections. The testis, seminal vesicle, and epididymis weights were all reduced in diabetic animals. Insulin injections raised all organ weights; however, only testis weights were fully restored. Levels of epididymal ABP activity were found to be higher in diabetic animals when expressed per mg protein. Similar patterns of organ weight loss and hormonal alterations were observed in semi-starved rats. However, epididymal levels of ABP activity were unaffected by the semi-starved condition. While weight loss should be taken into consideration when interpreting cause and effect relationships in streptozotocin-treated animals, epididymal ABP levels appear to be well correlated with the altered metabolic state characteristic of diabetes.
Diabetes 1983 Feb
PMID:Sertoli cell function in diabetic, insulin-treated diabetic, and semi-starved rats. 621 25

The concentration of glucose in the plasma of alloxan-diabetic rats was 23.4 +/- 0.86 mM (mean +/- SEM; n = 18), and the concentration of insulin was 11.4 +/- 1.67 microU/ml (mean +/- SEM; n = 17). The weights of the ventral prostate (0.45 +/- 0.03 vs. 0.72 +/- 0.04 g) and seminal vesicles (1.23 +/- 0.06 vs. 1.84 +/- 0.08 g) were decreased compared to control values and the rats lost body weight, but the weights of the testes were not significantly different from control values (3.14 +/- 0.08 vs. 3.23 +/- 0.14 g/pair). Similar changes were seen in streptozotocin-diabetic rats. The concentration of fructose (micromoles per g fresh wt) was greater in the coagulating gland of alloxan-diabetic (19.6 +/- 1.3; n = 17) than control rats (9.1 +/- 0.7; n = 18). The production of 14CO2 from D-[U-14C]glucose by spermatozoa or seminiferous tubules from diabetic rats was decreased compared to that in controls [28 +/- 3 vs. 53 +/- 6 nmol glucose converted/10(8) spermatozoa X 30 min (n = 8) and 0.81 +/- 0.03 vs. 1.08 +/- 0.03 mumol glucose converted/g fresh wt X 30 min (n = 7)]. There was no change in the production of lactate or 3HOH from D-[2-3H] glucose, and the presence of insulin (10 mU/ml) in the incubation had little effect. Rat epididymal spermatozoa took up 2-deoxy-D-glucose by a facilitated diffusion mechanism; the Km was about 0.2 mM, with a maximum velocity of about 0.10 nmol/10(6) spermatozoa X 10 sec. Neither alloxan-diabetes nor the presence of insulin (10 mU/ml) had an appreciable effect on these parameters.
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PMID:The effect of experimentally induced diabetes on the metabolism of glucose by seminiferous tubules and epididymal spermatozoa from the rat. 623 7

The effects of copper and insulin on lipogenesis and glucose tolerance were studied using diabetic, copper-deficient rats. Diabetes was induced by intraperitoneal injection of 50 mg streptozotocin/kg body weight to rats fed a sucrose-copper deficient diet for 7 weeks. Five days later the rats were injected intraperitoneally with [14C]glucose with either saline, insulin, copper, or copper plus insulin. The disappearance of serum [14C]glucose at 30, 60, and 120 min postinjection and the incorporation of [14C]glucose into lipid of epididymal fat 2 hr after administration were determined. The combined effect of copper and insulin significantly decreased peak blood glucose at 30 min and increased the incorporation of [14C]glucose into lipid in the epididymal fat pad when compared to either copper or insulin alone. The enhancement of glucose utilization may be due to a formation of a more stable complex which will increase insulin binding and/or decrease its degradation.
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PMID:Effect of copper or insulin in diabetic copper-deficient rats. 634 92

Rats were fed ad libitum diets containing a combination of commonly consumed highly palatable snack foods, a commercial stock diet, or had access to both diets for 10-11 weeks. Rats fed snack foods only had elevations in risk factors associated with heart disease and/or diabetes including serum cholesterol, insulin response to glucose, and serum glucose. Triglyceride levels were not affected by diet. Removable fat pad weights (perirenal and epididymal) were greater in rats fed snack foods than in rats fed only stock diet, even though total body weights were less. Liver glucose 6-phosphate dehydrogenase activity was not affected by diet, but malic enzyme activity was greater in rats fed snack foods only than in the other two groups. These results indicate that some risk factors associated with heart disease and/or diabetes can be elevated by feeding a diet containing commonly consumed snack foods.
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PMID:Effects of a combination of common snack foods on some risk factors in heart disease and diabetes in rats. 635 Apr 3

The dose-response characteristics of three skeletal muscles, three adipose tissue beds, and heart muscle to single i.v. injection of insulin were compared in vivo. Comparisons were made at 8 dose levels spanning the entire range for response by all tissues and for the integrated whole body response as reflected in the rate of disappearance of 3H-2-deoxyglucose from plasma. The insulin-sensitive tissues varied widely with respect to the magnitude of the maximal response and the sensitivity to insulin as judged by the effective dose 50% (ED 50). Among the muscles, a slow-twitch oxidative muscle, soleus, was more sensitive than the fast-twitch glycolytic muscle, extensor digitorum longus (EDL), while a mixed muscle, quadriceps femoris, displayed even lower sensitivity. Heart muscle sensitivity was comparable to EDL. Among the adipose sites, the rank order of sensitivity was subcutaneous greater than epididymal much greater than omental. The threshold for a detectable response to insulin was 0.013 U/kg rat.
Diabetes 1984 Feb
PMID:Insulin dose-response characteristics among individual muscle and adipose tissues measured in the rat in vivo with 3[H]2-deoxyglucose. 636 69

Pieces of rat epididymal fat tissue were maintained in a biochemically defined medium for 20 to 44 hours in either the absence or presence of a sulfonylurea at levels known to be effective in humans. Prolonged exposure of adipocytes to sulfonylureas did not influence the number of insulin receptors or their affinity to insulin or the ability of insulin to induce receptor loss (down-regulation). Also, the sulfonylureas did not influence the basal uptake of the D-glucose analogs 2-deoxyglucose and 3-O-methylglucose. However, exposure to these drugs resulted in a potentiation of the stimulatory effects of insulin on hexose transport at submaximal and maximally effective concentrations of insulin. The average potentiation was approximately 30%. In addition, sulfonylureas enhanced stimulation of hexose uptake by the insulin mimickers, hydrogen peroxide and vitamin K5. These oxidants are known to manifest insulin-like actions subsequent to insulin binding. Under conditions in which glucose transport was rate limiting, the conversion of glucose to carbon dioxide and the total lipids mirrored the findings of hexose uptake. However, at a glucose concentration of 50 mM, at which hexose transport is no longer rate limiting, sulfonylureas did not potentiate metabolism in th absence or presence of insulin. These results may help to explain the hypoglycemic action of the drug in view of the recent finding that a postreceptor deficit is present in noninsulin-dependent diabetes mellitus.
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PMID:Extrapancreatic effects of sulfonylureas. Potentiation of insulin action through post-binding mechanisms. 640 22


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