Chloroquine inhibits the insulin production of isolated pancreatic islets

Andersson, Arne; Olsson, Sten; Tjälve, Hans

doi:10.1016/0006-2952(80)90132-x

Cited by 15 publications

(8 citation statements)

References 24 publications

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“…This might slow down the effect on lysosomal cerebroside sulfotransferase in mouse compared to rat islets. No additional experiment was done with a longer incubation period because brefeldin A and chloroquine, used in long‐term experiments, lead to both structural and functional changes in the insulin‐producing beta cells (3, 33). Despite the differences when ob/ob and Lewis islets are compared, the major route for sulfatide synthesis in ob/ob mouse islets is through recycling, which supports that an altered metabolic pathway is not associated with lack of the C16:0 sulfatide isoform.…”

Section: Discussionmentioning

confidence: 99%

Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models

Blomqvist

Østerbye

Månsson

et al. 2003

APMIS

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Sulfatide (3'-sulfogalactosyl-ceramide) is a glycosphingolipid mainly located in the nervous system, but has also been found in the islets of Langerhans. Previous studies have suggested that sulfatide is involved in insulin processing and secretion. In this study, sulfatide expression and metabolism in pancreas and isolated islets of the type II diabetes models, ob/ob- and db/db mouse, was investigated using TLC-ELISA, metabolic labelling and electron microscopy. As in non-diabetic Lewis rat and human pancreas, sulfatide was located in secretory granules of the beta cells. However, the type II diabetic animal models and their background strains had an altered sulfatide expression, involving the lack of the C16:0 sulfatide fatty acid isoform, compared to non-diabetic Lewis rat, BALB/c mouse and human pancreatic tissue, in which the two dominating pancreatic sulfatide isoforms C16:0 and C24:0 are expressed. Correspondingly, in isolated ob/ob islets, sulfatide synthesis excluded the production of C16:0 sulfatide. Insulin administration to ob/ob mouse, which lowers beta cell activity, resulted in significantly increased sulfatide expression in pancreas (p=0.0003), but still no expression of the C16:0 sulfatide isoform. In vitro, the C16:0 sulfatide was shown to be the isomer involved in the preservation of insulin crystals. Thus, it is hypothesized that the selection of sulfatide isomers in pancreas might be a genetic factor contributing to disease development in type II diabetic animal models.

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Section: Discussionmentioning

confidence: 99%

Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models

Blomqvist

Østerbye

Månsson

et al. 2003

APMIS

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“…From the latter study, they concluded that although chloroquine does not influence glucose-induced release or intra-insular degradation of insulin, it interferes with the biosynthesis of insulin. An in vitro study [12] showed a marked decrease in the rate of glucose oxidation in the mouse islets of Langerhans suggesting that this may be due to the inhibition of mitochondrial electron transport, which would thereby inhibit insulin production. The results of that study indicated that the insulin content, release and biosynthesis of islets exposed to chloroquine were all markedly depressed.…”

Section: Discussionmentioning

confidence: 99%

“…According to previous reports, some authors suggested that the drug has inhibitory effect on metabolic pathways of glucose in parasites [8,9] where it was found to inhibit the uptake of glucose by schistosoma [10]. The drug was reported to decrease insulin and glucose levels in rats by interfering with insulin biosynthesis [11], decrease the rate of glucose oxidation in islets of Langerhans [12] and decrease fasting glucose level in rats treated with subchronic level of chloroquine [13]. Others suggested that chloroquine reduces intracellular insulin degradation in vitro [14] and in vivo [15] and inhibits 125 I-insulin degradation in the perfused rat liver [16].…”

Section: Introductionmentioning

confidence: 99%

“…According to previous reports, some authors suggested that the drug inhibits protein synthesis in bacteria by inhibition of RNA synthesis [21], of ribosome content of Bacillus megaterium [22], of amino acid uptake by the cell [23] and of polypeptide synthesis in the rat liver cell-free system [24]. Concurrently, it has been reported to inhibit protein biosynthesis in bovine [25] and rabbit retinal preparations [20], as well as in the mouse pancreatic islets [12]. Inhibition of hemedependent protein synthesis in malaria parasite [26] was observed.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Chloroquine on Glucose Metabolism

Gaafar

Khedr²,

Bashandy³

et al. 2011

Arzneimittelforschung

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The long- and short-term effects of chloroquine (CAS 54-05-7) on glucose metabolism in rats were assessed. The long-term chronic chloroquine administration (5 and 10 mg/kg b.w. 6 days a week for 6 months) caused a decrease in serum glucose, insulin, calcium, potassium and protein levels, while the glucagon level increased. The short-term acute effect of chloroquine administration (10 mg/kg b.w. 6 days for one week) caused an improvement in glucose tolerance as shown by the decrease in glucose and insulin curves after an oral glucose tolerance test. This was accompanied by an increase in insulin activity, corrected insulin response, and glucose tolerance parameter and a decrease in glucose and insulin areas. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased, too, indicating an increase which provides the needed energy for overcoming the injurious effect of chloroquine.

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“…Such key metabolic en zymes as glucose-6-phosphate dehydroge nase, alcohol dehydrogenase and succinate dehydrogenase have been shown to be inhib ited by chloroquine [1], Long-term and short-term chloroquine administrations to cultured rat pancreatic B cells have been reported to impair the specific functions of these insulin-producing cells [2], Short-term exposure resulted in a marked depression in insulin biosynthesis and release. A decreased rate of glucose oxidation, hence reduction in energy source, reported by Anderson et al [2] was thought to be due to an inhibition of mitochondrial electron transport by the drug [3] . Another recent study [4] has demon strated the ability of chloroquine to stimu late ATP hydrolysis in human erythrocytes incubated in the absence of glucose.…”

Section: Introductionmentioning

confidence: 99%

Effects of Perinatal Exposure of Albino Rats to Chloroquine

Mgbodile¹

1987

Neonatology

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The effects of perinatal exposure of Wistar-derived albino rats to chloroquine were studied. Chronic exposure to 10 mg/kg of chloroquine phosphate during intra-uterine and postnatal life resulted in a marked decrease in neonatal and postweaning body and organ weights. The fasting blood glucose level was significantly elevated at 8 weeks of age in animals exposed to chloroquine. The observed growth retardation suggested transplacental poisoning and poisoning through milk transfer. The elevation in blood sugar level could be a consequence of possible ultrastructural and biochemical alterations of pancreatic B cells.

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Chloroquine inhibits the insulin production of isolated pancreatic islets

Cited by 15 publications

References 24 publications

Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models

Selective lack of the C16:0 fatty acid isoform of sulfatide in pancreas of type II diabetic animal models

Effect of Chloroquine on Glucose Metabolism

Effects of Perinatal Exposure of Albino Rats to Chloroquine

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