Action of Toxic Drugs on Islet Cells

Cooperstein, S.J.; Watkins, Dudley

doi:10.1016/b978-0-12-187820-7.50021-8

Cited by 64 publications

(34 citation statements)

References 202 publications

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“…The inhibition of glucokinase (Fig. 2) by alloxan can provide an explanation for the inhibition of glucose-induced insulin secretion by alloxan and several other puzzling phenomena (Zawalich et al 1979), which were not compatible with any of the earlier hypo¬ theses (Cooperstein & Watkins 1981). All the characteristics elucidated in the present investiga¬ tion support this conclusion.…”

Section: Discussionsupporting

confidence: 77%

“…Alloxan is a diabetogenic agent (Webb 1966;Rerup 1970) and the mechanism of its selective pancreatic B-cell cytotoxic action has been pres¬ umed to be intimately related to the mechanism of glucose-induced insulin secretion (Cooperstein & Watkins 1981). It has therefore been widely used as a tool for the elucidation of mechanisms under¬ lying glucose-induced insulin secretion (Cooper¬ stein & Watkins 1981).…”

mentioning

confidence: 99%

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Glucokinase in pancreatic B-cells and its inhibition by alloxan

Lenzen

Tiedge

Panten

1987

Acta Endocrinologica

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Characterization of glucokinase in pancreatic B-cells from ob/ob mice and from rat liver revealed identical characteristics. A narrow substrate specificity; high Km values for the two substrates, D\ x=r eq-\ glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody. These characteristics distinguish glucokinase in soluble cytoplasmic fractions of pancreatic B-cells and liver from low Km hexokinases. Alloxan is a pancreatic B-cell cytotoxic agent, which has been widely used as a tool for the elucidation of the mechanisms of insulin secretion, because its inhibitory action on insulin secretion has been presumed to be intimately related to the mechanism of glucose-induced insulin secretion. Alloxan inhibited glucokinase but not hexokinase activity in cytoplasmic fractions of pancreatic B-cells and liver. The half maximal inhibitory concentration of alloxan was 5 \g=m\mol/l. Glucokinase activity was protected from alloxan toxicity only by D-glucose and D-mannose; the \g=a\ anomer of D-glucose provided significantly greater protection than the \ g=b\ anomer. The non-metabolizable sugar 3-0-methyl-D-glucose did not provide protection of glucokinase activity against inhibition by alloxan. Thus, inhibition of pancreatic B-cell glucokinase may contribute to the inhibition of glucose-induced insulin secretion by alloxan. These results support the contention that glucokinase regulates the metabolic flux rate through the glycolytic chain in the pancreatic B-cell and thereby generates the signal for glucose-induced

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Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 99%

Glucokinase in pancreatic B-cells and its inhibition by alloxan

Lenzen

Tiedge

Panten

1987

Acta Endocrinologica

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“…Diabetes was induced in adult wistar rats of either sex by a single intravenous injection of 45 mg/kg of STZ dissolved in citrate buffer (0.1 M, pH-4.5) [28]. Serum glucose levels were checked after 72 h. Animals with serum glucose levels >300 mg/ 100 ml were considered diabetic and were used for the study [29].…”

Section: Dose Calculationmentioning

confidence: 99%

Anti-diabetic activity of oryzanol and its relationship with the anti-oxidant property

Ghatak

Panchal

2012

Int J Diabetes Dev Ctries

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Experimental evidence suggests that oxidative stress induced by streptozotocin (STZ) damage the pancreatic beta cells and produce hyperglycemia in rats. The current study was initiated to investigate the effects of oryzanol (OZ), a commercially-important bioactive phytochemical isolated from crude rice bran oil (cRBO) against experimental diabetes as well as the antioxidant potential of the drug. OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Oral administration of OZ (50 and 100 mg/kg) reduced the blood glucose level in normal and in STZ (45 mg/kg, intravenous) diabetic rats in both single and multidose study. Oxidative stress produced by STZ was found to be significantly reduced by OZ when compared to control rats, as evident from a significant decrease in the extent of lipid peroxidation (LPO) and increased levels of enzymatic anti-oxidants such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the liver. The findings indicate that OZ possesses the potential to effectively ameliorate the oxidative stress induced by STZ and produce a reduction in blood glucose levels. However, further experiments at the clinical level are warranted to confirm the utility of OZ in the therapeutic management of diabetes mellitus.

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“…of alloxan monohydrate was employed to induce diabetes (Cooperstien and Walkins, 1981). After 72 h, animals with serum glucose levels higher than 250 mg/dl were considered diabetic and were included in the study (Perfumi and Tacconi, 1996).…”

Section: Effects Of Poe On Serum Glucose Levels In Alloxan Diabetic Rmentioning

confidence: 99%