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

The influence of diabetes and starvation on uracil nucleotide metabolism in muscle was studied. It was found that the uridine triphosphate (UTP) content of heart and diaphragm muscle was decreased in fasted and streptozotocin-diabetic rats and that insulin treatment of diabetic animals restored the UTP concentration to normal levels. The ATP content of heart tissue was not altered under these conditions. It was also demonstrated that hemidiaphragms from streptozotocin-diabetic rats synthesized less UTP from uridine in vitro than hemidiaphragms from normal animals. Uridine kinase activity of extracts of cardiac and skeletal muscle from fasted and diabetic rats was lower than the activity found in extracts from control animals. It was concluded that uracil nucleotide synthesis by the salvage pathway is decreased in experimental diabetes and fasting.
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PMID:Effect of diabetes and fasting on the uridine triphosphate content and uridine kinase activity of rat cardiac and skeletal muscle. 22 81

Elsewhere we have proposed that the rapid transient efflux of 32P orthophosphate that occurs when prelabeled pancreatic islets are exposed to nutrient secretagogues (the "phosphate flush") reflects one of the earliest steps in islet stimulus-secretion coupling. We have now shown that the "phosphate flush" is much smaller with islets from fetal rats 21 1/2 days old. This could be attributed to decreased cellular stores of radioactivity, especially inorganic orthophosphate (32P), at the onset of stimulation, which may have been due, in part, to the diminished ability of fetal islets to retain the radiophosphorus accumulated during the labeling period. Certain other differences in phosphate metabolism were also observed. With prelabeled islets from adult rats, exposure to 3.0 mg. per milliliter glucose effected acute increases in the tissue content of AT32P and GT32P. Comparable stimulation of prelabeled fetal islets with 3.0 mg. per milliliter glucose did not elicit detectable changes in the labeling of ATP or GTP. The findings indicate that selected aspects of phosphate metabolism may be immature in fetal islets and, perhaps, implicated in their obtunded secretion of insulin in response to stimulation with glucose.
Diabetes 1978 Jun
PMID:Phosphate metabolism and glucose-initiated efflux of phosphate ions in islets of fetal pancreas. 35 Jun 75

In animals the pyruvate dehydrogenase reaction is mainly responsible for the irreversible loss of glucose carbon by oxidation. Regulation of this reaction is shown to be a major determinant of glucose conservation in starvation and diabetes. Estimates of conservation in man in starvation and diabetes are reviewed. The pyruvate dehydrogenase complex is inhibited by products of its reactions; it is also regulated by a phosphorylation-dephosphorylation cycle catalysed by a kinase intrinsic to the complex and by a more loosely associated phosphatase. Inactivation is largely accomplished by phosphorylation of the tetrameric decarboxylase component (alpha2beta2) to alpha2Pbeta2. Complete phosphorylation produces the (alpha2P3)beta2 form. Both forms are completely reactivated by phosphatase action but the initial rate of reactivation of a complex containing alpha2Pbeta2 is approximately three times that of (alpha2P3)beta2. The proportion of active (dephosphorylated) complex is decreased in rat tissues by starvation and diabetes and in perfused rat heart by oxidation of fatty acids and ketone bodies. In adipose tissue in vitro, insulin increases the proportion of active complex and lipolytic hormones may decrease this proportion. It is suggested that rates of oxidation of lipid fuels may be a major determinant of the activity of pyruvate dehydrogenase in tissues in relation to the actions of insulin and lipolytic hormones and the effects of diabetes and starvation. Phosphorylation and inactivation of the complex are enhanced by high mitochondrial ratios of [acetyl-CoA]/[CoA], [ATP]/[ADP], [NADH]/[NAD+] and low concentrations of pyruvate, Mg2+ and Ca2+, and vice versa.
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PMID:Regulation of pyruvate oxidation and the conservation of glucose. 37 69

The levels of ATP, ADP, AMP, inorganic phosphate and 2,3-DPG have been determined in blood and liver of normal and streptozotocin-diabetic rats maintained for up to 11 months on a diet in which the sole carbohydrate source was either starch or sucrose. The feeding of sucrose to normal rats did not significantly alter the adenine nucleotide or phosphate content of the liver and blood. The diabetic state caused a reduction in the ATP, and an increase in AMP and phosphate content of the liver. The feeding of sucrose to the diabetic animals increased the blood phosphate level. The erythrocyte 2,3-DPG content was unaffected by the alterations of ATP and phosphate levels or by the diabetes.
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PMID:The effects of dietary sucrose and streptozotocin-diabetes on blood and liver constituents. 44 Jun 35

The intravenous injection of zinc or manganese chloride immediately before and 15 minutes after alloxan or dithizone prevented the usual hyperglycemia observed 24 hours after induction of diabetes. Injection of zinc chloride in alloxan diabetes led to normalization of sodium while zinc, copper, iron and magnesium remained high and calcium and potassium remained low as in alloxan. In case of dithizone diabetes, the administration of zinc salt led to an increase in serum zinc, magnesium and potassium and to a decrease in serum calcium while the sodium level returned to normal. Manganese plus alloxan led to a normalization of serum zinc, copper, potassium and sodium. In the case of dithizone plus manganese only magnesium was raised while the other elements were unchanged when compared to animals injected with dithizone only. Chromium and cobalt lowered the blood glucose to a certain extent however it did not affect most of the elements. The same changes occurred in all elements as with alloxan or dithizone alone. Pretreatment with ATP led to a normalization of serum zinc, copper, magnesium, sodium and potassium, while in case of iron it remained high and calcium remained low as that found in alloxan diabetic rats.
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PMID:Serum mineral changes due to exogenous ATP and certain trace elements in experimental diabetes. 44 5

Acute alloxan diabetes (3 days) in the rat resulted in a decreased ability of the isolated perfused working heart to respond to increased atrial filling pressure with normal systolic (aortic) pressure development, using a physiologic concentration of glucose (5 mM) as substrate. The diabetic heart also exhibited impaired cardiac output, which could be attributed entirely to decreased aortic output without any apparent effect on coronary flow. This decrease in ventricular performance was accompanied by a 40% reduction in glucose uptake and a 20% reduction in tissue ATP concentrations even though perfusate glucose levels remained at or near physiologic levels. Perfusion of hearts with 5 mM glucose plus 10(-8) M insulin, with 10 or 30 mM glucose, or 1 mM octanoate reversed the diabetes-related decrease in systolic pressure development, cardiac output, and tissue ATP content. These data demonstrate that the defect in cardiac performance with increased work loads associated with acute insulin deficiency is due to the relative inability of the heart to utilize physiologic concentrations of glucose as substrate for energy production.
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PMID:Cardiac performance of isolated perfused hearts from alloxan diabetic rats. 44 43

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

A 70-yr-old mildly diabetic white male was discovered to have an elevated level of serum free glycerol in the range of 75 mg/dl and to excrete about 13 g of free glycerol in the urine per 24 h. During a 24-h fast the urine glycerol loss increased to 21.5 g per 24 h. Studies carried out in vitro using leukocytes prepared from the patient's blood which were incubated with [14C]glycerol demonstrated an almost complete absence of glycerol oxidation to 14CO2 and of glycerol phosphorylation, in contrast to control studies with leukocytes collected from normal subjects. Homogenates of the patient's leukocytes contained negligible activity of ATP:glycerol phosphotransferase (glycerokinase EC 2.7.1.30) as measured by a direct spectrophotometric method. Marked hyperglycerolemia has thus far been detected in one brother and in one son of the daughter of this patient. This evidence suggests an x-linked recessive inheritance pattern of the trait. There is a high prevalence of diabetes mellitus in this family.
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PMID:Familial hyperglycerolemia. 61 10

Liver function tests were performed in severe and mild diabetic rats and under the influence of ATP. In mild diabetics the serum cholesterol was significantly increased, while in severe diabetes the serum cholesterol was significantly lower than in mild diabetes. The decreased serum cholesterol in severe diabetes may be an indication for the development of fatty liver. The serum alkaline phosphatase and serum bilirubin were significantly increased in both the severe and mild diabetic states, while the thymol turbidity test was insignificantly changed in both states of diabetes. Serum albumin was significantly decreased in 10 days mild diabetes, while it was insignificantly changed in 48 hrs severe diabetic animals. The effect of ATP was investigated in mild diabetes. ATP resulted in a significant increase in serum albumin and a decrease in total globulins with the resultant increase in A/G ratio. The serum alkaline phosphatase exhibited a significant reduction under the influence of ATP. The elevated cholesterol of mild diabetic rats remained significantly elevated and was not reduced by ATP, though the fat content of the liver showed a significant reduction. This may be due to more rapid mobilisation of fat from the liver under the influence of ATP. ATP showed no significant effect on serum bilirubin and thymol turbidity test. the histopathological examination of the liver revealed that administration of ATP to alloxan diabetic rats had a beneficial effect. It resulted in disappearrance of the fat globules from the liver cells.
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PMID:Effect of ATP on liver function tests in experimental diabetes. 65 50

During the first two thirds of gestation, the concentrations of UDPG, ATP, ADP, and Mg++ in human fetal liver remain constant, whereas the concentration of Pi decreases twofold and the G-6-P and AMP concentrations increase. Incubation of human fetal liver explants with glucagon or insulin did not alter the concentrations of any of these intermediates. ATP, ADP, and Pi are inhibitors of human fetal liver glycogen synthase D-form activity, while G-6-P and AMP and Mg++ are stimulators. Ca++ at concentrations of less than 0.1 mM was found to stimulate glycogen synthase D activity. This effect of Ca++ was also observed in "physiologic" mixtures containing UDPG, G-6-P, ATP, ADP, AMP, Pi, and Mg++ at concentrations found either in liver in utero or in explants. 45Ca++ efflux from perifused (rat) fetal liver explants was stimulated by glucagon. These data provide a picture of the metabolite regulation of human fetal liver glycogen synthase activity in which the D-form may largely control glycogen synthesis in utero and hormonal effects on glycogen synthase may be induced by effects of Ca++ on the D-form.
Diabetes 1975 Dec
PMID:Hormonal regulation of glycogen metabolism in human fetal liver. II. Regulation of glycogen synthase activity. 81 98


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