New Hypothesis of Insulin Secretion

Lacy, Paul E.; Howell, S. L.; Young, Donald A.; Fink, Christoph

doi:10.1038/2191177a0

Cited by 539 publications

(199 citation statements)

References 11 publications

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“…Colchicine has been shown to inhibit the secretory process in liver (2,10,(39)(40)(41) and other tissues (15,20,21,30,31,47) . It has been shown to have a disorganizing effect on Golgi structure in certain tissues (44) and to inhibit endocytosis in chondrocytes (33), fibroblasts (45), and macrophages (44).…”

mentioning

confidence: 99%

Effect of colchicine on the uptake of prolactin and insulin into Golgi fractions of rat liver.

Posner¹,

Verma²,

Patel³

et al. 1982

The Journal of Cell Biology

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In previous studies we have shown that 125I-labeled prolactin is taken up by a receptor-dependent process and concentrated in an intact form in Golgi elements from female rat liver (J. Biol. Chem., 1979, 254:209-214). In this study we have examined the effect of colchicine on this uptake process into Golgi elements. Colchicine [25 mumol (10 mg)/100 gm body wt] was injected intraperitoneally in adult female rats, and hepatic Golgi fractions were prepared at 1, 2, and 3 h postinjection. The enzyme recoveries and morphological appearance of fractions from colchicine-treated and control (alcohol alone) animals were similar. At times greater than 1 h after colchicine there was a marked (greater than 60%) inhibition of uptake of 125I-ovine prolactin (125I-oPRL) into Golgi light and intermediate fractions but no inhibition of uptake into Golgi heavy and plasmalemma elements. At times from 2 to 45 min postinjection, 125I-oPRL was extracted from Golgi elements and found to be largely intact as judged by rebinding to receptors. The inhibitory effect of colchicine was seen at doses ranging from 0.25 mumol to 25 mumol/100 g body wt. Vincristine also inhibited 125I-oPRL uptake into the Golgi light and intermediate fractions but lumicolchicine had no inhibitory effect. There was a smaller effect of colchicine both at early (1 h) and later (3 h) times on the extent and pattern of 125I-insulin uptake. Colchicine treatment did not produce a significant change in lactogen receptor levels in the Golgi fractions. These results demonstrate that colchicine treatment inhibited the transfer of prolactin into Golgi vesicular elements. The much smaller effect on insulin uptake suggests that there may be differences in the manner in which the two hormones are handled in the course of internalization.

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mentioning

confidence: 99%

Effect of colchicine on the uptake of prolactin and insulin into Golgi fractions of rat liver.

Posner¹,

Verma²,

Patel³

et al. 1982

The Journal of Cell Biology

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“…Although colchicine has been reported to impede secretory reactions in several tissues (3)(4)(5)(6)(7)(8)(9), it was initially difficult to reproduce these findings. Incubation of sensitized lung fragments under varied conditions in eight initial experiments with colchicine (0.0001-1 mM), and one experiment with vinblastine (0.01 mM) and podophylline (1 ,ug/ml) resulted in minimal suppression of the immunologic release ofhistamine and no inhibition of SRS-A release (Table I).…”

Section: Resultsmentioning

confidence: 89%

“…3). The immunologic release of histamine and SRS-A was totally suppressed for the initial 15 min after removal of isoproterenol, SRS-A release returned to control levels by 25 3 The effect of isoproterenol on the capacity of colchicine to suppress the immunologic release of histamine and SRS-A from human lung tissue. Untreated lung fragments and colchicine-primed lung fragments (0.1 mM, 60 min, 37°C) were incubated with 1 ,uM isoproterenol for 3 min, washed twice, and the antigen challenged 10 s to 60 min later.…”

Section: Resultsmentioning

confidence: 99%

“…These biochemical events translate the immunologic signal at the surface of the lung mast cell to the intracellular process of moving the mediator containing secretory granules toward the cell surface where sequential exocytosis (2) occurs. Functioning microtubules have been shown to be necessary for many secretory processes (3)(4)(5) including the nonimmunologic release of histamine from human peripheral leukocytes (7,8) and human lung tissue (9). It seemed possible, therefore, that a portion of the partially delineated biochemical sequence of events involved in the immunologic release process might relate to the assembly and function of microtubules.…”

Section: Introductionmentioning

confidence: 99%

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Human Lung Tissue and Anaphylaxis

Kaliner¹

1977

J. Clin. Invest.

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A B S T R A C T The addition of specific antigen to IgEsensitized human lung tissue causes the secretion of the mediators histamine and slow-reacting substance of anaphylaxis. The mechanisms by which increased levels of cyclic AMP suppress and increased levels of cyclic GMP enhance this secretory process were studied. Colchicine, an agent which disrupts many secretory reactions by binding to microtubules in their disassembled 6S form, was a relatively ineffective inhibitor of the antigen-induced release of mediators unless lung fragments were incubated at 4°C for 60 min to induce microtubular disassembly. As colchicine appeared to inhibit the immunologic secretion of mediators from human lung tissue most effectively after microtubular disassembly, the capacity of colchicine to modulate the release reaction indicated the state of microtubular assembly; inhibition by colchicine signaled a shift to the colchicine-sensitive 6S subunits whereas failure to inhibit suggested maintenance in the colchicine-resistant polymerized state.Exogenously added 8-Bromo-cyclic GMP prevented low temperature-facilitated colchicine suppression of mediator release suggesting that increased levels of cyclic GMP stabilize polymerized microtubules. Transiently increased cyclic AMP concentrations, either exogenously added as 8-Bromo-cyclic AMP or endogenously produced by isoproterenol, promoted colchicine suppression of mediator release suggesting that microtubular disassembly was produced. Direct measurement of cyclic AMP levels revealed parallel kinetics after isoproterenol stimulation between control and colchicine-treated lung fragments.The requirement for functional microtubules in the release reaction may occur after the antigen IgEstimulated activation of a serine esterase, energy

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“…Microtubules and microfilaments have been shown to be involved in the secretion processes of many glands: thyroid gland [ 11, pancreatic islets [2], adrenal medulla [3], anterior pituitary [4], parotid gland [ 51 and exocrine pancreas [6,7]. Most of these studies used drugs known to alter the structure of these cellular organelles.…”

Section: Introductionmentioning

confidence: 99%