Stimulation of Insulin Secretion by Theophylline

Turtle, John R.; Littleton, G. K.; Kipnis, David

doi:10.1038/213727a0

Cited by 174 publications

(72 citation statements)

References 17 publications

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“…Thus methylxanthines can increase cyclic AMP levels by releasing catecholamine (Wooten et al, 1973) and thus stimulating cyclic AMP synthesis and/or by inhibiting cyclic 3',5'-nucleotide phosphodiesterase (Butcher et al, 1965) and thus preventing cyclic AMP degradation. The cyclic AMP increases in fat cells and in the pancreas result in increased lipolysis (Butcher et al, 1965) and insulin secretion (Turtle et aL, 1967) respectively. Thus in the present study aminophylline increased both plasma UFA and insulin. These changes can exert mutual influences.…”

Section: Discussionmentioning

confidence: 99%

“…not only on the concentrations of tryptophan but also on those of tyrosine and phenylalanine in plasma and brain 3 h after the injection in order to see whether the effect was specific to tryptophan. Plasma insulin was also determined to see whether a relation exists between the amino acid changes and the effect of aminophylline on insulin secretion (Turtle et al, 1967). Figure 3 shows the concentration of total plasma tryptophan together with that of UFA and insulin.…”

Section: Behavioural Effects Ofaminophyllinementioning

confidence: 99%

“…The increased 5-HT turnover due to aminophylline is associated with an increase in brain tryptophan concentration (Curzon & Knott, 1974) which appears to be related to inhibition of cyclic AMP breakdown in fat cells (Butcher, Ho, Meng & Sutherland, 1975) leading to an elevation of UFA and hence of free tryptophan in the plasma. However, the catecholamine releasing (Wooten, Thoa, Kopin & Axelrod, 1973), insulin releasing (Turtle, Littleton & Kipnis, 1967) or other actions of aminophylline could also be involved.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

Curzon

Fernando

1976

British J Pharmacology

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1Aminophylline and other methylxanthines increase brain tryptophan and hence 5-hydroxytryptamine turnover. The mechanism of this effect of aminophylline was investigated. 2 At lower doses (t> 100 mg/kg i.p.) the brain tryptophan increase could be explained by the lipolytic action of the drug, i.e. increased plasma unesterified fatty acid freeing plasma tryptophan from protein binding so that it became available to the brain. 3 Plasma unesterified fatty acid did not increase when aminophylline (100 mg/kg i.p.) was given to nicotinamide-treated rats but as both plasma total and free tryptophan rose, a tryptophan increase in the brain still occurred. 4 The rise in brain tryptophan concentration following the injection of a higher dose of the drug (150 mg/kg i.p.) could no longer be explained by a rise of plasma free tryptophan as the ratio of brain tryptophan to plasma free tryptophan rose considerably. Plasma total tryptophan fell and the plasma insulin concentration rose. 5The increase of brain tryptophan concentration after injection of 150 mg/kg aminophylline appeared specific for this amino acid as brain tyrosine and phenylalanine did not increase. However as their plasma concentrations fell the brain/plasma ratio for all three amino acids rose. 6 The higher dose of aminophylline increased the muscle concentration of tryptophan but that of tyrosine fell and that of phenylalanine remained unaltered. The liver concentrations were not affected. 7 The aminophylline-induced increases of the ratio of brain tryptophan to plasma free tryptophan no longer occurred when the drug was given to animals injected with the fl-adrenoceptor blocking agent propranolol or the diabetogenic agent streptozotocin. 8 The changes in brain tryptophan upon aminophylline injection may be explained by (a) increased availability of plasma tryptophan to the brain due to increased lipolysis and (b) increased effectiveness of uptake of tryptophan by the brain due to increased insulin secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Behavioural Effects Ofaminophyllinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

Curzon

Fernando

1976

British J Pharmacology

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“…Indirect evidence has accumulated during recent years, indicating that cyclic AMP is important also for the release of insulin from the pancreatic beta cells [4,51, although the precise manner in which this nucleotide participates in insulin secretion is obscure.…”

Section: Introductionmentioning

confidence: 99%

Activation by glucose of adenyl cyclase in pancreatic islets of the rat

Grill

Cerasi

1973

FEBS Letters

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“…This effect of theophylline was augmented (30-to 40-fold increase) by pretreatment with an a-adrenergic blocking agent (phentolamine ), and was completely blocked by ^-adrenergic blockade (propranolol) (Turtle et al, 1967). The effect of a-receptor stimula tion might be mediated by a decrease in the level of cAMP, while 3-receptor effects could be mediated by an increase in cAMP (Robinson et al, 1967;Porte, 1967).…”

Section: Adenyl Cyclase System and Insulin Secretionmentioning

confidence: 95%

Suppression of insulin secretion during spontaneous and induced hypocalcemic states

Witzel

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Stimulation of Insulin Secretion by Theophylline

Cited by 174 publications

References 17 publications

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

Activation by glucose of adenyl cyclase in pancreatic islets of the rat

Suppression of insulin secretion during spontaneous and induced hypocalcemic states

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