Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenacylimidazolium compound LY177507 was shown by Harris et al. (Harris, R. A., Yamanuchi, K., Roach, P. J., Yen, T. T., Dominiani, S. J., and Stephens, T. W. (1989) J. Biol. Chem. 264, 14674-14680) to stimulate glycogen synthesis greatly in isolated rat hepatocytes. We extended studies with this compound, designated proglycosyn (Yamaguchi, K., Stephens, T. W., Chikadar, K., Depaoli-Roach, A., And Harris, R. A. (1991) Diabetes 40, (Suppl. 1) 102 (abstr.] employing hepatocytes from normal and streptozotocin diabetic rats. Proglycosyn is more effective than amino acids in stimulating glycogen synthesis. In cells incubated with glucose, lactate, or dihydroxyacetone the effect of glutamine and proglycosyn was synergistic. In cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, the stimulation by the two agonists was additive. Proglycosyn diverted the gluconeogenic flux from glucose to glycogen. The maximal rates of glycogen deposition attained in the presence of glutamine and proglycosyn from cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, where about 80 and 110 mumols/h/g of liver, respectively. Proglycosyn depressed glycogenolysis in hepatocytes of fed rats and stimulated glycogen synthesis from lactate and dihydroxyacetone. The incorporation of [U-14C]glucose and [U-14C]lactate in these cells occurred in the presence of glycogen breakdown or exceeded net production, indicating the occurrence of recycling of glycogen in hepatocytes of fed rats. Hepatocytes from fasted streptozotocin diabetic rats contained high levels of glycogen. Glycogenolysis was markedly depressed by proglycosyn. Glycogen synthesis from lactate and dihydroxyacetone in these cells was stimulated by glutamine and proglycosyn in a fashion similar to that in cells from fasted control rats, and the rates of glycogen synthesis were similar in cells of control and diabetic rats. With glucose as sole substrate, glutamine did not stimulate glycogen synthesis. When both agonists were present, there was a marked synergism and substantial glycogen formation. Streptozotocin diabetic rats prior to the onset of cachexia have a normal capacity for glycogen synthesis.
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PMID:Stimulation of glycogen synthesis by proglycosyn (LY177507) by isolated hepatocytes of normal and streptozotocin diabetic rats. 193 54

Changes in plasma glucose and glucose and glycogen content in fetal erythrocytes (FRBCs) were studied in rats between days 15 and 21 of gestation and in adult rats. Plasma and FRBC glucose concentrations increased during fetal life and were higher in erythrocytes than in plasma. Glycogen was higher in FRBCs than in adult erythrocytes and tended to decrease from day 15 to 19 of gestation and to increase again on day 21. When FRBCs were incubated in vitro in different glucose concentrations to study their capacity to compensate for changes in plasma glucose concentration, younger cells showed better glucose-buffering capacities. Glucose and glycogen levels in FRBCs increased when they were incubated in high-glucose medium, and the glycogen concentration reached was higher in the early fetal stage than by the end of gestation. Nevertheless, adult erythrocytes accumulated more glycogen in high-glucose medium than cells from any of the fetal-aged erythrocytes. When glucose was injected intraperitoneally into fetuses of different ages, there was an increase of 3.7 microM/ml in glucose concentration in blood from the umbilical artery and 2.5 microM/ml in blood from the umbilical vein. FRBCs buffered some of this change, as evident by an increase in glycogen content. Again, buffering capacity was greater for erythrocytes in younger fetuses. Epinephrine diminished glycogen concentration in venous FRBCs on days 19 and 21 of gestation even in hyperglycemia. Insulin diminished glucose concentration in arterial plasma on days 17 and 21 of gestation, but there were no changes in glucose and glycogen in FRBCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Oct
PMID:Compensation by fetal erythrocytes of plasma glucose changes in rats. 221 72

The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status.
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PMID:Liver pathology in morbidly obese patients with and without diabetes. 153 87

Glycogen nephrosis, i.e. the Armanni-Ebstein lesion which manifests itself by intracellular accumulation of beta-glycogen has been studied in two groups of streptozotocin diabetic rats and compared to controls. One diabetic group was left untreated and the other diabetic group received pancreatic islet transplantation after 4 weeks duration of diabetes. The kidneys were studied after another 4 week period with normoglycemia. In the non-transplanted diabetic animals glycogen containing tubules comprised 43% of the distal tubule length in the cortex but in the transplanted animals no abnormal, glycogen containing cells could be recovered at the light microscope level. Measurements of the total distal tubule length in the non-transplanted diabetic animals showed that the distal tubules increased in length by 24%. In the transplanted diabetic animals distal tubule length remained the same as in the non-transplanted diabetic animals in spite of normalization of the tubular morphology. This finding could possibly be responsible for the incomplete normalization of kidney weight after treatment.
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PMID:Regression of glycogen nephrosis in experimental diabetes after pancreatic islet transplantation. 313 43

In rat hepatocytes, the basal glycogen synthase activation state is decreased in the fed and diabetic states, whereas glycogen phosphorylase a activity decreases only in diabetes. Diabetes practically abolishes the time- and dose-dependent activation of glycogen synthase to glucose especially in the fed state. Fructose, however, is still able to activate this enzyme. Glycogen phosphorylase response to both sugars is operative in all cases. Cell incubation with the combination of 20 mM glucose plus 3 mM fructose produces a great activation of glycogen synthase and a potentiated glycogen deposition in both normal and diabetic conditions. Using radiolabeled sugars, we demonstrate that this enhanced glycogen synthesis is achieved from both glucose and fructose even in the diabetic state. Therefore, the presence of fructose plays a permissive role in glycogen synthesis from glucose in diabetic animals. Glucose and fructose increase the intracellular concentration of glucose 6-phosphate and fructose reduces the concentration of ATP. There is a close correlation between the ratio of the intracellular concentrations of glucose 6-phosphate and ATP (G6-P/ATP) and the activation state of glycogen synthase in hepatocytes from both normal and diabetic animals. However, for any given value of the G6-P/ATP ratio, the activation state of glycogen synthase in diabetic animals is always lower than that of normal animals. This suggests that the system that activates glycogen synthase (synthase phosphatase activity) is impaired in the diabetic state. The permissive effect of fructose is probably exerted through its capacity to increase the G6-P/ATP ratio which may partially increase synthase phosphatase activity, rendering glycogen synthase active.
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PMID:Glycogen synthesis from glucose and fructose in hepatocytes from diabetic rats. 314 17

An initial transient hyperglycemia was seen in mice injected with asparagine, fluoroacetate, hydroxylamine, or malonate plus methionine, whereas an initial triphasic blood glucose response and a transient "secondary" hyperglycemia were exhibited in those injected with hydroxylamine plus arsenite, and a delayed hypoglycemia was observed in those treated with fluoroacetate or arsenite. The glucose-induced insulin secretion was significantly decreased in isolated pancreatic islets incubated with hydroxylamine plus arsenite. Light and electron microscopy, pyroantimonate technique, and X-ray microanalysis disclosed mitochondrial damage, degeneration, and necrosis among the beta-cells in the islets of mice injected with hydroxylamine plus arsenite. Glycogen depletion and microvesicular fatty change were seen in the liver of mice treated with fluoroacetate, arsenite, or hydroxylamine plus arsenite. These observations support the view that inhibition of the activity of citric acid cycle enzymes and associated reactions in the beta-cells play a role in the induction of diabetic features.
Diabetes 1988 Jan
PMID:Structural beta-cell changes and transient hyperglycemia in mice treated with compounds inducing inhibited citric acid cycle enzyme activity. 327 58

Earlier histochemical findings from our laboratory have shown that a lectin (agglutinin) from Griffonia simplicifolia, which reportedly binds to terminal N-acetylglucosamine residues in glycoconjugate oligosaccharides also shows affinity for glycogen. In the present study, the lectin was conjugated to horseradish peroxidase and applied to paraffin sections of kidney from streptozotocin-diabetic rats, insulin-treated and untreated, and age-matched control rats. Griffonia simplicifolia agglutinin II detected glycogen in cortical ascending thick limbs of untreated diabetic rat kidneys as early as 24 h following injection of streptozotocin. The number of stained cells increased steadily so that by day 14 of diabetes the lectin reacted with nearly all of the cells lining ascending thick limbs in the cortex and adjacent outer stripe of the outer medulla. Glycogen was never identified in the inner medullary stripe. Comparison of Griffonia simplicifolia agglutinin II and periodic acid-Schiff staining revealed that periodic acid-Schiff could not clearly detect glycogen until 14 days following injection of streptozotocin, which substantiated earlier claims that Griffonia simplicifolia agglutinin II might be a more sensitive indicator of glycogen than periodic acid-Schiff. The distribution of glycoconjugate containing terminal N-acetylglucosamine stainable with the lectin was unchanged in diabetic kidneys. Griffonia simplicifolia agglutinin II served in the present study to further characterise the sequence of abnormal glycogen accumulation in streptozotocin-diabetic rat kidneys. In addition, it was shown that the lectin's ability to antedate periodic acid-Schiff detection of glycogen has utility in histochemical investigations in diabetes.
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PMID:Lectin detection of renal glycogen in rats with short-term streptozotocin-diabetes. 342 97

The role of fetal insulin in placental glycogen accumulation, which occurs despite insulin deficiency in maternal diabetes, was studied in rats. Streptozotocin was injected into fetuses of non-diabetic and streptozotocin-diabetic mothers on days 19.5 and 20.5 of gestation, causing fetal hypoinsulinaemia and pancreatic insulin depletion. Placental glycogen content of either 1.6 mg/g in non-diabetic rats or 6.5 mg/g in diabetic rats was not affected by fetal streptozotocin treatment. Glycogen distribution was also measured in the placenta to assess the effect of fetal hypoinsulinaemia on glycogen content in its fetal segment. The glycogen concentration ratio between the fetal and maternal segments in diabetic rats was approximately 0.3 and increased to approximately 0.5 in diabetic rats, without being affected by fetal hypoinsulinaemia. There was no significant effect of fetal hypoinsulinaemia on the activities of placental glycogen synthase or glycogen phosphorylase, both in non-diabetic and diabetic rats. Fetal hypoinsulinaemia was associated, however, with a marked decrease in fetal liver glycogen together with a decrease in fetal liver weight, which was more pronounced than the decrease in fetal body weight. Administration of insulin to the streptozotocin-treated fetuses restored the impaired glycogen synthesis (measured by incorporation of U-[14C]-glucose and 3H2O in the fetal liver) without affecting glycogen synthesis in the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fetal diabetes in rats and its effect on placental glycogen. 392 71

The effects of prior high-intensity cycle exercise (85% VO2 max) to muscular exhaustion on basal and insulin-stimulated glucose metabolism were studied in obese, insulin-resistant, and normal subjects. Six obese (30.4% fat) and six lean (14.5% fat) adult males underwent two separate, two-level hyperinsulinemic-euglycemic clamp studies (100-min infusions at 40 and 400 mU/m2/min), with and without exercise 12 h earlier. Carbohydrate oxidation was estimated by indirect calorimetry using a ventilated hood system, and endogenous glucose production by D-(3-3H)-glucose infusion. Glycogen content and glycogen synthase activity (GS %l) were measured in vastus lateralis muscle biopsies before and at the end of each insulin clamp procedure. After exercise, the obese and lean subjects had comparably low muscle glycogen concentrations (0.10 versus 0.08 mg/g protein, respectively), and equal activation of muscle GS activity (54.4 versus 45.3 GS %l, respectively). In the obese subjects, insulin-stimulated glucose disposal was increased significantly, but not totally corrected to normal. In both groups there was a comparable increase in nonoxidative glucose disposal (NOGD), whereas glucose oxidation was decreased and lipid oxidation was increased. Thus, the major effect of prior exercise was to increase insulin-stimulated glucose disposal in the obese subjects and to alter the pathways of glucose metabolism to favor NOGD and decrease glucose oxidation. No correlation was found between the exercise-induced increase in GS %l and NOGD, except in the normal subjects during maximal insulin stimulation. Thus, glycogen synthase activity does not appear to be rate-limiting for NOGD at physiologic insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Oct
PMID:Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. 393 Mar 21

In the islets of rat pancreas, steroid diabetes induced by triamcinolon-acetonid led to glycogen infiltration of B cells. Ultracytochemically, glycogen was detected within 24 hours after glucocorticoid administration using the periodic acid-silver proteinate method according to Maxwell (1978). Glycogen was primarily located in the cytoplasm of granulated B cells but could also be detected in the halo of the secretory granules of these cells. The amount of glycogen increased during the course of the 5 day experiment. The A, D, and PP cells were free of glycogen.
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PMID:Ultrastructural distribution of glycogen in pancreatic islets of steroid diabetic rats. 639 90


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