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

Alloxan diabetes, starvation of rabbits within one day and administration of hydrocortisone during 5 days did not cause distinct alterations in the total activity of pyruvate kinase in kidney cortex. At the same time pronounced alterations in the isozyme spectra were observed: the L-type activity of pyruvate kinase was decreased and the M2-type of activity was increased. The total activity and the isozyme content of pyruvate kinase were only slightly altered in starvation of rabbits during 3 or 10-16 days and after administration of protamine-Zn-insulin during 3 days. Hydrocortisone caused variable effects on the pyruvate kinase isozymes from kidney cortex, depending on periods of administration.
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PMID:[Effect of insulin and hydrocortisone on the isoenzyme composition of pyruvate kinase in the rabbit kidney]. 102 50

The enhancement of long-chain fatty acid oxidation and ketogenesis in the perfused rat liver, whether induced acutely by treatment of fed animals with anti-insulin serum or glucagon, or over the longer term by starvation or the induction of alloxan diabetes, was found to ba accompanied by a proportional elevation in the tissue carnitine content. Moreover, when added to the medium perfusing livers from fed rats, carnitine stimulated ketogenesis from oleic acid. The findings suggest that the increased fatty acid flux through the carnitine acyltransferase (carnitine palmitoyl-transferase; palmitoyl-CoA:L-carnitine O-palmitoyltransferase; EC 2.3.1.21) reaction brought about by glucagon excess, with or without insulin deficiency, is mediated, at least in part, by elevation in the liver carnitine concentration.
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PMID:Role of carnitine in hepatic ketogenesis. 106 Jan 16

The present study was undertaken to determine whether alterations in ketone body utilization and hepatic production, independent of the FFA load, were also involved in the development of fasting ketosis. Plasma Beta-OH butyric acid (Beta-OHB) increased to 2.5-4.5 mM and plasma FFA to 1,000-1,400 muEq/L. in normal weight individuals after five to seven days' starvation and in obese subjects after ten to fourteen days' fasting. Acute elevations fo the plasma FFA greater than 1,500 muEq/L. for sixty minutes in fed normal weight and obese subjects with a fat meal-heparin regimen resulted in peak elevations of plasma Beta-OHB (0.25-0.45mM), only 10 percent of that seen during fasting. When plasma FFA were lowered acutely during fasting with the antilipolytic agent Pyrazole to control levels (400-600 muEq/L.), plasma Beta-OHB decreased 35 plus or minus 5 per cent. Comparable lowering of plasma FFA in normal weight or obese starved subjects given dexamethasone to maintain elevated fasting plasma insulin levels resulted in an 87 plus or minus 3 per cent decrease in plasma Beta-OHB. Similar studies in obese fasted subjects pretreated with an intravenous infusion of insulin (1.0 U/hr. for eight hours) before receiving Pyrazole resulted in a 65 plus or minus 5 per cent decrease in plasma Beta-OHB. Plasma Beta-OHB half-life, determined after injections of 12 gm. Beta-OHB, increased significantly during fasting (110 plus or minus 15 minutes) and was decreased when the fasting subjects were maintained on dexamethasone (65 plus or minus 7 minutes). These studies indicate that accelerated hepatic ketogenesis during starvation is a result of both enhanced activity of the enzymatic system(s) involved in ketone body production as well as an increased FFA load. The increase in plasma Beta-OHB during fasting reflects not only an accelerated rate of hepatic ketogenesis but also an impairment of peripheral utilization, both processes apparently being sensitive to insulin. Diabetes 24:10-16, January, 1975.
Diabetes 1975 Jan
PMID:Physiologic mechanisms in the development of starvation ketosis in man. 112 May 41

Two isoenzymes of pyruvate kinase--PK-1 and PK-2 were obtained from the cortical layer of rabbit kidney by the method of chromatography on DEAE-cellulose. Starvation of rabbits for 10--16 days and alloxan diabetes produced no significant changes in the specific activity of PK in the soluble fraction obtained from the cortical layer of rabbit kidney. However, there were significant shifts in the isoenzymatic spectrum of the PK of the kidneys in rabbits with alloxan diabetes: the activity of the PK-1 increased considerably and significantly, and the isoenzyme PK-2 disappeared almost completely.
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PMID:[Pyruvate kinase isoenzymes in the kidneys of rabbits with insular insufficiency]. 112 47

1. The in vitro transport of 3-0-methyl-D-glucose was measured in the small intestine of obses-hyperglycemic (ob/ob) mice and their lean littermates, fed or fasted for 48 hrs. 2. Transport was much increased in the jejunum of obese animals and, to a lesser extent, in obese mice on a chronic restricted diet. 3. Kinetic studies indicate that the Vmax of transport was significantly greater in obese than in lean mice, whether fed or fasting. Fasting increase the Vmax in lean but not in obese animals. These changes were more prominent in the jejunum. The apparent Km of transport was the same in all four groups. 4. These findings are discussed in relation to the increase in intestinal absorptive functions in diabetes and in some conditions of food restriction or starvation. The results are consistent with the hypothesis that the effects of diabetes and of starvation on intestinal sugar transport reflect an alteration in the same controlling factor.
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PMID:Sugar transport in the small intestine of obese hyperglycemic, fed and fasted mice. 118 64

The insulin secretory response to a sudden and sustained intravenous glycemic stimulus was measured in three groups of dogs whose antecedent carbohydrate intake ranged from zero to 300 or more grams daily. Insulin outflow rate from the pancreaticoduodenal vein was measured every minute for ten minutes, then at increasing intervals through sixty minutes. It was found that starvation erased the first phase of the biphasic insulin response shown by dogs on ordinary carbohydrate intake and that high-carbohydrate intake abolished the trough between the two phases. The data suggest that, during truly physiologic stimulation of insulin secretion, the latter represents the final stage of a continuum of hormonal synthesis, storage, and release, rather than emanating from one of two separate pools of fast-versus-slow insulin secretion.
Diabetes 1975 Dec
PMID:Influence of antecedent carbohydrate intake on the biphasic insulin response to intravenous glucose. 119 12

The synthesis of ketone bodies by intact isolated rat-liver mitochondria has been studied at varying rates of acetyl-CoA production and of acetyl-CoA utilization in the Krebs cycle. Factors which enhanced the rate of acetyl-CoA production caused an increase in the fraction of acetyl-CoA which was incorporated into ketone bodies. On the other hand, it was found that factors which stimulated the formation of citrate lowered the relative rate of ketogenesis. It is concluded that acetyl-CoA is preferentially used for citrate synthesis, if the level of oxaloacetate in the mitochondrial matrix space is adequate. The intramitochondrial level of oxaloacetate, which is determined by the malate concentration and the ratio of NADH over NAD+, is the main factor controlling the rate of citrate synthesis. The ATP/ADP ratio per se does not affect the activity of citrate synthase in this in vitro system. Ketogenesis can be described as an overflow of acetyl-groups: Ketone-body formation is stimulated only when the rate of acetyl-CoA production increases beyond the capacity for citrate synthesis. The interaction between fatty acid oxidation and pyruvate metabolism and the effects of long-chain acyl-CoA on mitochondrial metabolism are discussed. Ketone bodies which were generated during the oxidation of [1-14C] fatty acids were preferentially labelled in their carboxyl group. This carboxyl group had the same specific activity as the acetyl-CoA pool, whereas the specific activity of the acetone moiety of acetoacetate was much lower, especially at low rates of ketone-body formation. The activities of acetoacetyl-CoA deacylase and the hydroxymethylglutaryl-CoA (HMG-CoA) pathway were compared in soluble and mitochondrial fractions of rat- and cow-liver in different ketotic states. In rat-liver mitochondria, both pathways of acetoacetate synthesis were stimulated upon starvation or in alloxan diabetes. In cow liver, only the HMG-CoA pathway was increased during ketosis in the mitochondrial as well as in the soluble fraction.
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PMID:Aspects of ketogenesis: control and mechanism of ketone-body formation in isolated rat-liver mitochondria. 119 5

1. Phosphoenolpyruvate carboxykinase was assayed by three methods: (i) incorporation of H(14)CO(3) (-) into oxaloacetate: (ii) conversion of oxaloacetate into phosphoenolpyruvate, subsequently assayed enzymically; and (iii) transfer of (32)P from [gamma-(32)P]GTP to oxaloacetate. 2. Enzyme activity is increased in liver and epididymal adipose tissue in alloxan-diabetes and starvation, and in kidney in starved, acidotic and steroid-treated animals. 3. The ratios of the ;back' to the ;forward' reactions in liver, kidney and epididymal adipose tissue are different and characteristic of each tissue; they differ markedly from values reported for the purified mitochondrial enzyme. 4. The ratio of the ;back' to ;forward' reaction in any one tissue is constant in adrenalectomized, diabetic, acidotic and steroid-treated animals. 5. In starved animals, the ratio is increased in liver and kidney, but decreased in epididymal adipose tissue. 6. Administration of l-tryptophan results in an acute (1h) increase in activity measured in the ;forward' direction alone in liver and epididymal adipose tissue, but not in kidney.
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PMID:The activity of phosphoenolpyruvate carboxykinase in rat tissues. Assay techniques and effects of dietary and hormonal changes. 122 Jun 93

A study was made of 16 patients with the initial mild form of diabetes mellitus in whom the immunoreactive insulin (IRI) indices in glucose loading pointed to a good reactivity of the beta-cells of the insular apparatus of the pancreas. As a result of the dietetic treatment or therapy with saccharolytic oral preparations diabetes proved to become compensated but the IRI indices were unchanged. In patients with adiposity there was seen an increase in the concentration of blood IRI and a reduction of the reaction of beta-cells to the administration of glucose. A course of treatment by dosaged starvation (a loss of weight by an average of 11.5 kg) caused no improvement in the IRI indices was less pronounced, and the treatment by diet with limited caloric value led to improvement of the IRI indices.
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PMID:[The influence of effective treatment of diabetes mellitus and obesity on the plasma concentration of immunoreactive insulin]. 122 84

The role of glucagon in regulating peripheral tissue metabolism in man was assessed in the present studies. To do this, glucagon was infused for two hours into the brachial artery to produce a high but physiologic increment in the glucagon content of arterial blood supplying ipsilateral tissues. Metabolic effects on muscle and on subcutaneous adipose tissue plus skin were sought in seven overnight-fasting subjects and seven subjects starved briefly (60 hours). In the overnight-fasted group the infusion increased bassl glucagon concentration by 1,216 pg./ml. but was without effect on forearm tissue metabolism of glucose, lactate,glycerol, or amino acids. Starvation significantly reduced basal insulin (11.0 to 7.4 muU./ml.) and increased endogenous glucagon (116 to 134 pg./ml.). Basally, there was substantial ketone utilization and a decrease in glucose consumption by both muscle and subcutaneous adipose tissue plus skin. The glucagon infusion increased basal glucagon by 784 pg./ml. Muscle balances of glucose, lactate, acetoacetate, amino acids, and glycerol were unaffected. The metabolism of glucose, lactate, acetoacetate, glycerol, and free fatty acids by subcutaneous adipose tissue plus skin was also unchanged. It is concluded that physiologic increments of glucagon lasting two hours are without effect on forearm tissues in overnight-fasted and briefly starved man.
Diabetes 1976 Feb
PMID:Metabolism of forearm tissues in man. Studies with glucagon. 124 74


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