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

The effect of experimental diabetes on hepatic drug metabolism was studied in male Holtzman rats. Treatment of animals with streptozotocin and 6-aminonicotinamide, both agents which produce an insulin-deficient animal, caused prolongation of hexobarbital sleeping times and inhibition of the rate of metabolism of both hexobarbital and, to a lesser extent, aniline in vitro. Treatment of animals with N-methylacetamide, a diabetogen which does not cause insulin deficiency in the animal but rather produces an insulin-resistant state, did not affect the metabolism in vitro of either hexobarbital or aniline. Neither insulin nor any of the diabetogenic agents had any direct effect on drug metabolism in vitro. Furthermore, hepatic microsomal protein and cytochrome P-450 contents were not significantly different in any of the diabetic animals from those of the control animals. Hyperglycemia produced by glucose infusion did not affect the metabolism of hexobarbital in vitro. The effects of streptozotocin and 6-aminonicotinamide appeared to be at least partially due to the presence of an inhibitor in the liver cytosol which correlated with elevated hepatic cyclic AMP concentrations.
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PMID:Effect of experimental diabetes on drug metabolism in the rat. 1 20

Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin containing 3 mg./ml. glucose and 0, 200, 400, or 800 microU./ml. of rat insulin, and the glucose-6-phosphate (G6P) and 6-phosphogluconate (6PG) contents were determined by enzymatic cycling. In response to a rise in the concentration of insulin, the 6PG/G6P ratio decreased. A close relationship was observed between this decrease of 6PG/G6P ratio and the net insulin release, the absolute rate of glucose oxidation via the pentose phosphate cycle, and the NADPH/NADP ratios measured under similar conditions. The results suggest that exogenous insulin, directly or indirectly, regulates the pentose cycle activity in the pancreatic islets at the G6P dehydrogenase step.
Diabetes 1977 Sep
PMID:6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin. 1 30

The aim of the present investigation was to examine the fetal and maternal blood glucose and insulin response following glucose infusion to the mother. The studies were performed on 11 primigravid patients with a gestational age of 38-40 weeks during the first stage of labor. Glucose was given intravenously by a bolus injection of 330 mg/kg body weight, followed by a glucose infusion of 27.5 mg/kg/min for 60 min. Glucose concentration, immuno-reactive insulin (IRI), pH and base excess of the maternal and fetal blood were measured before and during maternal glucose load. Maternal blood glucose rose within 10 min. up to 280.0 mg% (SD 25.9). This level could be fairly maintained throughout the experiment. The maternal glucose was after 60 min. infusion 326.5 mg% (SD 46.9). Fetal glucose concentration rose continuously from 65.8 mg% (SD 5.8) at control to 249.2 mg% (SD 23.3) after 60 min. The increase of maternal and fetal glucose was associated with an elevation of immuno-reactive insulin (IRI). The maternal insulin was 24.0 micronU/ml (SD 8.0). It was scattered over a wide range (55.4 micronU/ml-217.1 micronU/ml) after 60 min. glucose infusion. The fetal insulin was 17.0 micronU/ml (SD 5.2) at control and rose by 86.5% (SD 80.5) after 60 min. glucose load. One case of a mother with a subclinical diabetes mellitus deviated where the fetal insulin rose from 26.0 micronU/ml at control to 215.6 micronU/ml after 60 min. infusion. The increase of insulin per glucose rise was correlated to fetal body weight. During glucose infusion to the mother of both, fetal and maternal, acid base parameters remained unchanged. From these observations it may be concluded that in the human fetus insulin secretion following a single glucose load is generally low, however, it increases in cases where the maternal insulin response to glucose load is abnormal. This might be related to a chronic stimulation by glucose of the fetal pancreatic islet cells in poorly controlled diabetic and possibly prediabetic patients.
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PMID:Fetal and maternal blood glucose, insulin and acid base observations following maternal glucose infusion. 1 72

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
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PMID:[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. 2 43

Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells.
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PMID:An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics. 2 96

The lipoprotein-lipase activity (LPLA) in the abdominal, subcutaneous, adipose tissue was studied in a random sample (n = 69) of 60-year-old men. A new method for the quantification of LPLA was applied. The mean value was 67 mU/g when expressed per gram (wet weight) of adipose tissue. Several subjects within the lower part of the range of adipose-tissue LPLA values had low concentrations of serum-triglycerides (S-TG). There was no correlation between the LPLA and S-TG concentrations in the fasting state. Among the 69 subjects, four had newly detected diabetes mellitus and had significantly lower LPLA in the adipose tissue than the control group. The fat-cell size and the LPLA per gram of adipose tissue were not correlated. Thus, obesity without diabetes mellitus does not imply a low LPLA concentration in adipose tissue. The variation of the concentration of adipose-tissue LPLA in the fasting state in this population was explained only to a minor extent by the variation of S-insulin and blood-glucose parameters, when analysed statistically by a stepwise multiple-regression technique.
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PMID:Lipoprotein-lipase activity in subcutaneous, adipose tissue in healthy subjects: variation of activity in a population of 60-year-old men. 3 Jan 95

The rat hepatic stearoyl-CoA desaturation decreased by 3.7-fold in streptozotocin-induced diabetes. Insulin treatment of diabetic rats increased the enzyme activity by 7-fold. In marked contrast to glucose administration, fructose feeding in diabetic rats resulted in 20-fold stimulation of stearoyl-CoA desaturation, although both carbohydrates stimulated stearoyl-CoA desaturation in normal rats. Measurement of the microsomal electron transfer components showed no significant changes in the NADH-cytochrome b5 reductase activity or in the concentration of cytochrome b5. However, the activity of the terminal desaturase changed in a parallel fashion as the amount of terminal desaturase reflect changes in the overall desaturation. Supplementation of various microsomes with the saturating amount of purified terminal desaturase resulted in the formation of similar amounts of catalytically active complex and increased the stearoyl-CoA desaturation to the same level suggesting that the changes in the amount of terminal desaturase reflect changes in the overall desaturation. The results support the suggestion that both insulin and the intermediates of carbohydrate metabolism are involved in the regulation of terminal desaturase.
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PMID:Regulation of rat hepatic stearoyl coenzyme A desaturase. The roles of insulin and carbohydrate. 3 88

In the presence of glucose (2 mg/ml), leucine (10 mM) noticeably increased islets' NADPH contents as well as the NADPH:NADP ratio; the changes occurred as soon as 1 min after its addition. NADH concentrations were also increased by leucine. The NADPH:NADP ratio as well as insulin release stimulated by glucose plus leucine were markedly decreased by methylene blue. The thiol oxidants diamide and tert-butyl hydroperoxide also inhibited insulin secretion in response to glucose plus leucine. Employing the perfused pancreas technique, the insulin-releasing action of p-chloromercuribenzoate was further enhanced by leucine. The combined effects were inhibited by tert-butyl hydroperoxide, however. Our data suggest that the insulin-releasing action of leucine depends on the islets' NADPH and reduced glutathione (GSH); in addition, leucine may contribute to insulin secretion by increasing the islet NADPH:NADP ratio and the NADH:NAD ratio. From the data, we assume that the observed increase of NADPH may lead via GSH to an increase in the number of such thiol groups in the beta-cell membrane, which are believed to be related to stimulation of insulin release and, thus, to increase the sensitivity of the beta-cell to stimulation by glucose and/or leucine.
Diabetes 1979 Jun
PMID:Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released--interactions in vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate. 3 18

Factors that influence hemoglobin (Hb)A(Ic) synthesis by intact erythrocytes were studied in vitro. After incubation cells were lysed, and hemoglobins were separated by isoelectric focusing on polyacrylamide slab gels and quantitated by microdensitometry. HbA(Ic) increased with time, glucose concentrations (5-500 mM), and incubation temperature (4 degrees -37 degrees C). Low temperatures allowed prolonged incubations with minimal hemolysis. At 4 degrees C HbA(Ic) increased linearly with time for 6 wk; after incubation at the highest glucose concentration, HbA(Ic) comprised 50% of total hemoglobin. Insulin (1 and 0.1 mU/ml) did not affect HbA(Ic) synthesis in vitro. In addition to glucose, galactose and mannose, but not fructose, served as precursors to HbA(Ic). A good substrate for hexokinase (2-deoxyglucose) and a poor hexokinase substrate (3-O-methylglucose), were better precursors for HbA(Ic) synthesis than glucose, suggesting that enzymatic phosphorylation of glucose is not required for HbA(Ic) synthesis. Autoradiography after erythrocyte incubation with (32)P-phosphate showed incorporation of radioactivity into HbA(Ia1) and A(Ia2), but not HbA(Ib), A(Ic), or A. Acetylated HbA, generated during incubation with acetylsalicylate, migrated anodal to HbA(Ic) and clearly separated from it. Erythrocytes from patients with insulinopenic diabetes mellitus synthesized HbA(Ic) at the same rate as controls when incubated with identical glucose concentrations. Likewise, the rate of HbA(Ic) synthesis by erythrocytes from patients with cystic fibrosis and congenital spherocytosis paralleled controls. When erythrocytes from cord blood and from HbC and sickle cell anemia patients were incubated with elevated concentrations of glucose, fetal Hb, HbC, and sickle Hb decreased, whereas hemoglobins focusing at isoelectric points near those expected for the corresponding glycosylated derivatives appeared in proportionately increased amounts.
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PMID:Synthesis of hemoglobin Aic and related minor hemoglobin by erythrocytes. In vitro study of regulation. 3 12

The activity of enzymes with a regulatory function in the pathways of glycolysis, gluconeogenesis, NADPH generation and fatty acid synthesis was measured in the placenta and liver of rats. Compared with the liver, a high activity of pyruvate kinase was found in the placenta, indicating a high glycolytic potential; a small capacity for gluconeogenesis was also present and a moderate to low activity of enzymes associated with lipogenesis. The activity of all placental enzymes fell from day 15 to 20 of gestation irrespective of the pathway they represented. The pattern of decline continued when the gestation was prolonged up to day 26 by the administration of chorionic gonadotropin. The rates of activity disappearance over 11 days of gestation differed for each enzyme, with half-lives ranging from 2.7 days for NADP-malate dehydrogenase to 7 days for glucose-6-phosphate dehydrogenase. In contrast, the activity of hepatic enzymes either remained unchanged or showed individual adaptation to the advancing pregnancy. The regression in placental metabolic capacity after day 15 of gestation was also evident by the decrease in glucose uptake and its channelling to lactate, CO2, glycerol and fatty acids. In addition, placental ageing was associated with triglyceride accumulation, mainly due to the decrease in free fatty acid oxidation. Treatment of pregnant rats with several hormones, while markedly affecting the hepatic enzyme activities, failed to induce appreciable changes in the corresponding placental enzymes. This was illustrated in the case of triiodothyronine treatment. Similarly, insulin deficiency induced by streptozotocin failed to elicit adaptive changes in placental enzyme activities typical of diabetes like those occurring in the maternal liver; some converse responses in the placenta were attributed to hyperglycaemia. On the other hand, responses in some fetal liver enzymes were suggestive of fetal hyperinsulinaemia. These observations indicate that placental enzymes are not susceptible to endocrine regulation and imply that placental metabolism is largely independent of the physiopathological alterations affecting the maternal organism. The gradual activity decreases with gestation suggest that the enzyme complement of the placenta, once developed, is designed to last through its limited lifespan without continuous replenishment. Within this context, no mechanism seems to operate to ind1ce the adaptive synthesis of individual enzymes, and the age of the placenta appears to be the primary factor determining its enzyme activity and metabolic performance.
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PMID:Regulation of placental enzymes of the carbohydrate and lipid metabolic pathways. 3 55


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