Diabetogenic Effect of<scp>l</scp>-Asparaginase

Khan, Amanullah; Adachi, Mitsuo; Hill, Joseph M.

doi:10.1210/jcem-29-10-1373

Cited by 19 publications

(12 citation statements)

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“…Also, the small differences in plasma half-life (800 IU/kg, 19 h ; 1,400 IU/kg, 19.5 h, and 200 IU/kg, 18 h) would not seem to be sufficient to indicate either differential antibody formation or explain the peculiar dose-response observations. It should be noted that the incidence of toxicity reported in the present experiments is higher and occurs at a lower dose than those recently reported elsewhere (6,13). This variability may be related to differences either in the enzyme preparations or the strain of rabbits, or both.…”

Section: Discussioncontrasting

confidence: 64%

“…Clinically, many instances of pancreatitis have been reported (3), suggesting a direct alteration of the organ. However, in the present experiments, and those of Khan et al (6), the hyperglycemia was pro duced in the absence of any histological changes in the pancreas. The increases observed in BUN levels may be indicative of accelerated protein catabolism or impaired function of the kidney.…”

Section: Discussioncontrasting

confidence: 49%

“…The hyperglycemia following endotoxin has been reported to be due to increased catecholamine levels and could be blocked by such an agent as ergotamine (14). Although Tettenborn et al (13) reported variable results, ¿-aspara ginase has been reported to increase blood glucose levels both clinically (5) and experimentally (6). The mechanism of the ¿-asparaginase-induced hyperglycemia has not as yet been determined.…”

Section: Discussionmentioning

confidence: 99%

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A Comparison of Some Pharmacological Effects of Escherichia coli (E. coli) L-Asparaginase and E. coli Endotoxin in Rabbits

Herman¹,

Mhatre²,

Cooney³

et al. 1973

Pharmacology

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Escherichia coli (E. coli) endotoxin and E. coli L-asparaginase produced diarrhea, rapid respiration and nasal discharge. L-asparaginase caused a greater incidence of tremors, muscle fasciculations and ultimate convulsions than endotoxin. The maximal incidence of L-asparaginase toxicity (40–45 %) occurred after 800 or 1,400 IU/kg. Endotoxin toxicity was observed within 24 h, whereas L-asparaginase intoxication developed after 24 h. The blood pressure in animals displaying severe L--asparaginase toxicity was similar to that monitored in the control animals, whereas severe hypotension was found in endotoxin-intoxicated animals. L-asparaginase and endotoxin induced increases in blood glucose and urea nitrogen. The blood urea nitrogen levels returned to control levels by 72 h in surviving animals. Endotoxin also produced elevations in serum glutamic pyruvic transaminase and serum glutamic oxaloacetic transaminase levels. Endotoxin and L-asparaginase produced some histopathological changes in the lung, kidney, liver and spleen. The alterations in the liver and kidney appeared to be more severe after endotoxin treatment. Significant decreases in plasma levels of calcium and magnesium and an increase in plasma phosphorus levels were noted in L-asparaginase-intoxicated animals. These plasma ions were not altered by endotoxin treatment. Thus, the pharmacological effects of L-asparaginase observed in rabbits appear to differ in many respects from that of endotoxin.

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Section: Discussioncontrasting

confidence: 64%

Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Comparison of Some Pharmacological Effects of Escherichia coli (E. coli) L-Asparaginase and E. coli Endotoxin in Rabbits

Herman¹,

Mhatre²,

Cooney³

et al. 1973

Pharmacology

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“…Steroid therapy has been implicated in contributing to L-asp-induced diabetes [6,12]. However, 3% of pa tients who did not receive concomitant steroids developed L-asp-induced IGT as well [3].…”

Section: Discussionmentioning

confidence: 99%

Glucose Metabolism in Children with Acute Lymphoblastic Leukemia Treated according to Two Different L-Asparaginase Schedules

et al. 1984

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Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.

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“…Khan et al [1] found a transient diabeto genic effect of intravenous L-asparaginase in all the rabbits they treated with a single dose higher than 10,000 IU/kg. Further investigations proved that together with transient deterioration of glucose tolerance, occasionally with hyperglycemic coma, low levels of circulating insulin were present [2.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Endocrine Function in Leukemic Children Treated with L-Asparaginase

Meschi¹,

B²,

Gf³

et al. 1981

Horm Res

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The effect of arginine infusion on blood glucose and plasma levels of insulin, C-peptide and glucagon has been studied in leukemic children before and after treatment with L-asparaginase (10,000 U/m²/day for 10 days). Therapy induced a significant reduction in basal and peak blood glucose, insulin and C-peptide levels, while glucagon was unmodified. The conserved C-peptide-insulin molar ratio suggests the interference of L-asparaginase with proinsulin synthesis. In conclusion our results prove a decreased insulin reserve with a preserved, although reduced, beta-cell function.

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Diabetogenic Effect ofl-Asparaginase

Cited by 19 publications

References 0 publications

A Comparison of Some Pharmacological Effects of <i>Escherichia col</i><i>i</i> (<i>E. col</i><i>i</i>) <i>L</i>-Asparaginase and <i>E. coli</i> Endotoxin in Rabbits

A Comparison of Some Pharmacological Effects of <i>Escherichia col</i><i>i</i> (<i>E. col</i><i>i</i>) <i>L</i>-Asparaginase and <i>E. coli</i> Endotoxin in Rabbits

Glucose Metabolism in Children with Acute Lymphoblastic Leukemia Treated according to Two Different <i>L</i>-Asparaginase Schedules

Pancreatic Endocrine Function in Leukemic Children Treated with <i>L</i><i>-</i>Asparaginase

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