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

The oxygen dissociation curve shifted less to the right in venous blood draining from muscle in eight insulin-deficient diabetics working at a constant submaximal workload than in seven normal controls (28.7 mm. Hg vs. 30.8 mm Hg; P less than 0.05). This diminution of the in-vivo Bohr effect at the muscle tissue level during exercise in diabetics was due to a significantly smaller decrease of venous blood pH (down to 7.33 vs. 7.27 in normals; P less than 0.05), probably a consequence of an latered muscle metabolism in insulin deficiency. Although no glucose was taken up, even during exercise, and less lactate was produced by insulin-deficient muscle (P less than 0.05), the differences in venous blood pH appeared to be brought about mainly by a different CO2 production of the exercising muscle in the two groups. The response of Krebs cycle activity to exercise in insulin-deficient muscle might have been inadequate, as suggested by the increased 3-hydroxybutyrate/acetoacetate ratio in the venous blood observed in the normal controls but not in the diabetics. Furthermore, proportionally less of the arterial ketone body concentration was utilized by the working muscle in the insulin-deficient diabetics. Changes in erythrocyte 2,3-diphosphoglycerate did not contribute to the differences in the in-vivo Bohr effect.
Diabetes 1976
PMID:Muscle metabolism during rest and exercise: influence on the oxygen transport system of blood in normal and diabetic subjects. 0 24

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

1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.
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PMID:Glycerolkinase--a regulatory enzyme of gluconeogenesis? 18 91

Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.
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PMID:Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes. 20 May 11

Glucose utilization and the conversion of glucose to lactate, CO2, glycogen and lipids are decreased in the aorta from diabetic rats and rabbits. In addition the incorporation of amino acid into protein is reduced in diabetic rat aorta. The metabolic changes produced by diabetes are counteracted by insulin treatment, but there is a time lag of about 2 days before the effect of insulin treatment appears. The membrane transport of glucose in smooth muscle is carried out by a specific transport system of the facilitated diffusion type. A rate limiting influence of membrane transport on glucose metabolism is found in bovine mesenteric arteries and rabbit colon smooth muscle. In these preparations the influence of glucose concentrations on glucose metabolism is most pronounced in the range 0-11.1 mmol exhibiting saturation at higher glucose concentrations. Insulin in a high concentration (0.1 U/ml) has acute (less than or equal to 3 h) metabolic effects in vitro on smooth muscle which are qualitatively similar to those in skeletal muscle, but are weaker and appear later. The threshold concentration for the acute metabolic effects of insulin on smooth muscle in vitro is 10-100 times above the physiological levels, indicating a low acute sensitivity to insulin.
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PMID:Influence of diabetes on metabolism of vascular smooth muscle. 27 64

Six normal weight subjects without any heredity of diabetes (group 1), 3 obese subjects with normal (group 2) and 9 with pathological carbohydrate tolerance (group 3) were characterized by a 2-h glucose infusion test. Adipose tissue fragments were obtained from the abdominal wall by surgical biopsy under intracutaneous anesthesia. Adipocytes were isolated by collagenase digestion and incubated in buffer containing [1-14C] glucose and different concentrations of insulin. The metabolic effect of insulin was expressed as percent increase above control 14CO2 production. Maximal CO2 raised to 207 +/- 25% and 154 +/- 9% in groups 1 and 2, respectively. These values were significantly higher than in obese subjects displaying a pathological carbohydrate tolerance (group 3; 119 +/- 6%). A negative correlation was found between blood glucose levels and biological activity of insulin on adipocytes. The results suggest that insulin sensitivity of target tissue seems to play an important role in development of carbohydrate intolerance.
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PMID:Relationship between carbohydrate tolerance, insulin secretion, and insulin sensitivity of isolated fat cells from obese protodiabetics. 36 Jul 50

An "endoneurial" preparation from a rabbit tibial nerve fascicle was used to study the ability of peripheral nerve axons and Schwann cells to derive their composite energy requirements from glucose, D-beta-hydroxybutyrate, or albumin-bound palmitate, and the effects of insulin in vitro on their composite glucose utilization. Samples incubated with 5 mM glucose for 2 h maintained a stable O2 uptake and P-creatine and ATP concentrations, and they exhibited a slight increase in P-creatine/creatine ratio (the electron microscopic appearance of the preparation was previously shown to be unaltered under these conditions). The rate of glucose oxidation required to account for the O2 uptake accounted for 61% of the glucose uptake. In samples incubated without substrate for 2 h, a marked fall in tissue glucose was associated with a 50% decrease in O2 uptake and with decreases in P-creatine, ATP, and in the P-creatine/creating ratio. In medium lacking glucose but containing 5 mM DL-beta-hydroxybutyrate, a stable rate of D-beta-hydroxybutyrate uptake was observed, and acetoacetate production accounted for only a small fraction; significant decreases in O2 uptake or ATP were prevented, and, although P-creatinde and the P-creatine/creatine ratio fell, they remained significantly higher than after incubation without substrate. An efficient blood-nerve barrier to albumin is known to exist. Medium containing albumin-bound palmitate with molar ratios or palmitate/albumin of 1 or 2 (highest FFA concentration, 1.32 meq/L) failed to prevent decreases in P-creatine, ATP, and in the P-creatine/creatine ratio during incubations without glucose; the associated O2 uptakes suggested that the tissue is susceptible to respiratory uncoupling and depression son exposure to albumin-blund palmitate as compared with non-neural tissue. Insulin (100 or 1000 microU/ml) had no detectable effects on glucose utilization in the endoneurial preparation during 2-h incubations with 5 mM glucose or (U-14C) glucose. In contrast, in epineurial tissue from rabbit sciatic nerve, insulin (100 micronU/ml) increased (U-14C) glucose incorporation into CO2 and total lipid. The neural components of peripheral nerve are probably dependent on glucose as their major substrate for energy production and respiration under most physiologic conditions in which elevated plasma ketone body concentrations are absent; their composite glucose utilization is not subject to acute, direct regulation by insulin in concentrations that might reasonably be derived from plasma insulin of pancreatic origin.
Diabetes 1979 Oct
PMID:In vitro studies of the substrates for energy production and the effects of insulin on glucose utilization in the neural components of peripheral nerve. 47 82

This study was undertaken to ascertain whether enhanced oxidation of intracellular lipids could explain the impaired carbohydrate metabolism of diabetes. Pieces of diaphragms removed from diabetic (60--75 mg/kg streptozotocin i.v.) and control rats were incubated for 1 h with palmitate-1-14C. Tissue lipids from one piece were separated on silicic acid columns and the amount and specific activity of free fatty acids (FFA), triglycerides (TG) and phospholipids (PL) were measured. 14CO2 production was also assessed in some experiments. The other pieces of tissue were incubated for a subsequent hour (without radioactivity) at which time measurements of tissue lipid content and specific activity and 14CO2 production were again performed. FFA incorporation into CO2, tissue TG and PL was normal. TG content was moderately and PL content was slightly reduced in diabetic tissue. Changes in diaphragm TG and PL content and specific activity during the 2nd h of incubation strongly suggested that most of the 14CO2 produced during this period was derived from TG. Approximately 25% of tissue TG in both control and diabetic muscle was oxidized to CO2 during the 2nd h of incubation. In diaphragms from diabetic rats, (+)-octanoylcarnitine (an inhibitor of FFA oxidation) decreased TG oxidation considerably but had no effect on the impaired glucose uptake. Thus, these data do not support the hypothesis that the glucose-fatty acid cycle (utilizing either extra- or intracellular lipids) may account for the altered carbohydrate metabolism of diabetic muscle.
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PMID:Lipid metabolism by muscle of diabetic rats. 48 67

Seven patients suffering from maturity on-set diabetes mellitus were given orally 100 mg of 14C-labelled butylbiguanide, specific activity 1.40 or 1.23 muCi/mg, resp. Three days before oral administration, two of the patients had received an i.v. injection of 50 mg butylbiguanide labelled with 120 muCi 14C. The radioactivity in the blood of the patients was followed up during the first 12-h period after administration of the drug. For determination of the radioactivity in the urine aliquots of three 24-h portions were measured. Furthermore, the radioactivity was checked of each individual sample of faeces for the first 72 h after administration. The radioactivity in the exhaled air was also measured. By comparison of the excretion after i.v. and oral application an absorption efficiency of 90% to 92% was calculated. Butylbiguanide is almost exclusively and fast excreted via the kidney. 86.5% of the i.v. administered material was eliminated within 24 h and 88.1% within 3 d in the urine of a person without kidney disease. Elimination through faeces was negligible, 0.2% in a person without kidney disease and 0.7% in a patient with renal insufficiency. The data obtained from the exhaled air show that there is only a negligible break-down of butylbiguanide, if any, to CO2 in man.
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PMID:[Distribution and excretion of 14c-butylbiguanide in man (author's transl)]. 58 7

Cerebral blood flow (CBF) was studied at normocapnia and after a challenge with 5% CO2 in 59 diabetic patients and 28 controls. There was a significant age-related decline in CBF in both groups, which suggests that diabetes does not affect the rate of decrease of CBF with age. After CO2 challenge CBF increased in most of the controls; in the patients CBF increased in 23, decreased in 26, and remained stable in 10. Thus the reactivity of cerebral blood vessels in diabetics is altered. Diabetics have diminished cerebrovascular reserve and are thus at increased risk of cerebrovascular disease because they are unable to compensate when necessary with an increased CBF.
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PMID:Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity. 68


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