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

Methods are described for maintaining hypophysectomized rats (model for panhypopituitarism). Prolactin-secreting pituitary tumors can be induced in rats or mice by administration of estrogens; thyroid stimulating hormone-secreting tumors will occur in some mice after thyroid ablation by radioactive iodine. Estrogens in hamsters usually produce intermediate lobe tumors of the pituitary associated with hypothalamic degeneration. Sex hormone-secreting adrenal tumors can follow surgical gonadectomy in mice. Spontaneous corticoid-secreting adrenal tumors may occur spontaneously in Osborne-Mendel rats. Secretory gonadal tumors have been induced by transplantation of a gonad into the spleen of a gonadectomized host. Both secretory and non-secretory ovarian tumors can be produced by irradiation or chemical carcinogens in mice. In some mice, secretory testicular tumors can be produced by estrogen administration. Thyroid tumors can be induced in rodents by various kinds of goitrogens and irradiation. Parathyroid hyperplasia may occur with spontaneous renal disease in rats. A syndrome simulating diabetes mellitus can occur in rare strains of mice or can be induced by chemical destruction of the islets of Langerhans with alloxan.
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PMID:Experimental endocrinopathies. 17 62

Tests were set up on 59 albino male-rats with reproduced functional overstress and depletion of the insular system of the pancreas thorough a long-term (for 50, 100 days) peroral introduction of glucose (2 g/100 g body weight, every other day) and with and alloxan-induced diabetes (achieved by poisoning the animals with a 2.5% alloxan solution, 15 mg/100 g administered in a single dose intraperitoneally). A comparison of the data obtained ascertained the presence of a number of similar pathobiochemical changes in the metabolism, viz. hyperglycemia, an increase of the free cholesterol fraction, a diminution of the bound cholesterol fraction and a fall of the insulin-like activity (ILA) in the blood serum, a rise in glycogen and beta-lipoproteids in the liver; morphologically--a reduced count of Langerhan's islands beta-cells, less intensive colouration of the specific granulation in their cytoplasma manifestations of vacuolar and granular dystrophy of the liver. Further tests were staged on 23 rabbits involving a long-term introduction of glucose (in amounts of 25 g/kg every other day) and a cholesterol-induced atherosclerosis (by administering 0.2 g/kg of cholesterol in oil, daily), which also showed similar changes in the figures of the carbohydrate and fat-lipoids metabolism, such as hyperglycemia, an increased level of total lipids, cholesterol and its fractions, beta-lipoproteids, a fall of ILA in the blood serum, as well as variations in the morphological picture of the aortic wall. The above findings suggest that a protracted administration of glucose can produce both diabetogenic and atherogenic effects.
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PMID:[Diabetogenic and atherogenic effects of glucose]. 17 88

1. Starvation increases the activity of cytosolic P-enolpyruvate carboxkinase in rabbit liver some 4-5 fold but does not alter the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase or glucose-6-phosphatase.2. Alloxan-induced diabetes increases the activities of cytosolic P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase approx. 6-, 2- and 2-fold, respectively. Again the activity of mitochondrial P-enolpyruvate carboxykinase is not altered. 3. Administration of mannoheptulose rapidly increases blood glucose levels and also causes a significant increase in cytosolic P-enolpyruvate carboyxkinase activity within 4 h. The activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase are not affected. 4. Administration of hydrocortisone also increases blood glucose levels and the activities of cytosolic P-enolpyruvate carboxykinase and glucose-6-phosphatase are significantly increased within 12h. Again, mitochondrial P-enolpyruvate carboxykinase and fructose-1,6-diphosphatase activities remain unaffected. 5. The observations that (A) the activity of cytosolic P-enolpyruvate carboxykinase responds to more situations conducive to gluconeogenesis than do the activities of mitochondrial P-enolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase, and (B) cytosolic P-enolpyruvate carboxykinase activity is rapidly adaptive under appropriate circumstances, suggests that this particular enzyme's activity plays an important role in the regulation of gluconeogenesis in rabbits.
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PMID:Dietary and hormonal regulation of some enzyme activities associated with gluconeogenesis in rabbit liver. 17 42

Supplementation of rat lymphocyte cultures with plasma from alloxan-diabetic rats produced a dose-dependent suppression of mitogen-induced blastogenic responses. Viability measurements indicated that this inhibition was not due to a direct cytotoxic effect of alloxan-diabetic plasma on rat mononuclear leukocytes in vitro. This inhibition was not explained by hyperglycemia alone and was observed when blastogenesis was induced in vitro by phytohemagglutinin (PHA), concanavalin A (con A), or allogeneic cells. Peripheral blood lymphocytes from alloxan-diabetic rats appeared to be more sensitive than normal cells to the inhibitory effect of diabetic plasma. Heating at 56 degrees for 60 minutes produced only a partial loss of the inhibition by diabetic plasma. Alloxan-diabetic rat plasma promoted an increased accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in mononuclear leukocytes. Insulin (1 and 100 muU./ml.) in vitro enhanced PHA-induced blastogenesis but failed to reverse the inhibition caused by diabetic plasma. Ultrafiltration through a cellulose dialysis membrane with an exclusion size of 12,000 molecular weight did not remove the inhibitory factor(s). These results indicate that a depressed cellular immune response is produced during an insulin-deficient diabetic state. The suppressed in-vitro blastogenic response of lymphocytes from alloxan-diabetic rats appears to involve some circulating inhibitory factor(s) in diabetic plasma. This inhibition may be explained, in part, by the ability of diabetic plasma to elevate cyclic AMP in mononuclear leukocytes.
Diabetes 1976 Jul
PMID:Inhibition of lymphocyte blastogenesis by factor(s) in alloxan-diabetic rat plasma. 17 6

The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mM) or dichloroacetate (1mM) increased the proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart, presumably by inhibiting the pyruvate dehydrogenase kinase reaction. Alloxan-diabetes markedly decreased the proportion of active dehydrogenase in hearts perfused with pyruvate or dichloroacetate. 3. The total activity of pyruvate dehydrogenase in mitochondria prepared from rat heart was unchanged by diabetes. Incubation of mitochondria with 2-oxo-glutarate plus malate increased ATP and NADH concentrations and decreased the proportion of active pyruvate dehydrogenase. The decrease in active dehydrogenase was somewhat greater in mitochondria prepared from hearts of diabetic rats than in those from hearts of non-diabetic rats. Pyruvate (0.1-10 mM) or dichloroacetate (4-50 muM) increased the proportion of active dehydrogenase in isolated mitochondria presumably by inhibition of the pyruvate dehydrogenase kinase reaction. They were much less effective in mitochondria from the hearts of diabetic rats than in those of non-diabetic rats. 4. The matrix water space was increased in preparations of mitochondria from hearts of diabetic rats. Dichloroacetate was concentrated in the matrix water of mitochondria of non-diabetic rats (approx. 16-fold at 10 muM); mitochondria from hearts of diabetic rats concentrated dichloroacetate less effectively. 5. The pyruvate dehydrogenase phosphate phosphatase activity of rat hearts and of rat heart mitochondria (approx. 1-2 munit/unit of pyruvate dehydrogenase) was not affected by diabetes. 6. The rate of oxidation of [1-14C]pyruvate by rat heart mitochondria (6.85 nmol/min per mg of protein with 50 muM-pyruvate) was approx. 46% of the Vmax. value of extracted pyruvate dehydrogenase (active form). Palmitoyl-L-carnitine, which increased the ratio of [acetyl-CoA]/[CoA] 16-fold, inhibited oxidation of pyruvate by about 90% without changing the proportion of active pyruvate dehydrogenase.
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PMID:Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. 18 Sep 74

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

Normal male rats were made chronically diabetic by injection of alloxan or acutely diabetic by injection of anti-insulin serum. The concentration of cyclic AMP in epididymal adipose tissue was increased approximately 2 1/2-fold 24 h after alloxan administration and up to 7-fold 72 h post-alloxan. Treatment of alloxan-diabetic rats with insulin for 4 h completely suppressed lipolysis but only partially suppressed cyclic AMP levels; 6 h following insulin treatment cyclic AMP levels were normal. When segments of the epididymal fat bodies were incubated in vitro the high cyclic AMP levels were not maintained but instead decreased spontaneously. Addition of insulin to the incubation media decreased lipolysis in tissues of diabetic rats to levels measured in tissues of normal rats and accelerated the decline in cyclic AMP levels but did not return cyclic AMP levels to normal. Rats rendered acutely insulin deficient by injection of anti-insulin serum showed increased plasma glucose and free fatty acid levels and increased adipose tissue free fatty acid, and cyclic AMP levels 30 min following injection of the antiserum. Plasma glucagon levels increased but not until 2 h following anti-insulin serum, thereby excluding the possibility that an increment in plasma glucagon is the primary stimulus for the acceleration of lipolysis in diabetes. These data are consistent with the view that control of adipose tissue cyclic AMP levels in situ is an important physiologic action of insulin.
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PMID:Adenosine 3',5'cyclic monophosphate in adipose tissue of diabetic rats. 18 24

Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration.
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PMID:Alloxan diabetic neuropathy: electron microscopic studies. 18 54

Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes.
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PMID:Alloxan cytotoxicity in vitro. Inhibition of rubidium ion pumping in pancreatic beta-cells. 19 15

Liver protein kinase was determined in the absence and presence of cAMP4. Experimental alloxan diabetes resulted in a decrease in total protein kinase (+cAMP) and an increase in the activity ratio (-cAMP) divided by (+cAMP) in liver. Insulin treatment of diabetic rats reversed the observed changes in protein kinase in liver. Glucagon administered in vivo to normal rats caused an increase in the activity ratio and a decrease in total protein kinase activity in liver. The changes are similar to those in diabetes. A decrease in the ratio of insulin to glucagon in diabetes may account for the changes in protein kinase observed.
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PMID:Effect of experimental diabetes and glucagon on cAMP-dependent protein kinase in rat liver. 19 20


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