The Diphasic Effect of Vincristine on Glucose-Induced Insulin Secretion and Glucose Tolerance in the Intact Rat*

Shah, Jayendra H.; Udomphonkul, Nikom; Edwards, Gary; Hurks, Charles

doi:10.1210/endo-105-4-1041

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…Our previous 20 and present studies have demonstrated that (1) at 10 min after vincristine (0.15 mg/kg) treatment, glucose-induced insulin release was potentiated, but (2) at 60 and 120 min after vincristine treatment, glucose-induced insulin release was inhibited and glucose tolerance was impaired. In contrast, in the present study arginine-induced insulin release was not potentiated at 10 min nor inhibited at 60 and 120 min after vincristine treatment.…”

Section: Discussionmentioning

confidence: 51%

“…Such a time-related potentiating effect of vincristine was also observed at 10 min after its administration in our previous in vivo studies. 20 If the integrity of microtubules is important for glucose-induced insulin release 14 -15 then the potentiating effect of vincristine on glucose-induced insulin release cannot be explained by microtubular disruption caused by vincristine.…”

Section: Discussionmentioning

confidence: 99%

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Dissociation of the Effects of Vincristine on Stimulated Insulin Release and the Pancreatic β-Cell Microtubular Structures in the Intact Rat

Shah¹,

Stevens²,

Sorensen³

1981

Diabetes

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We have recently shown that in the intact rat, at 10 min after vincristine treatment, glucose-induced insulin release and glucose tolerance were potentiated, but at 60 and 120 min after vincristine treatment, glucose-induced insulin release and glucose tolerance were significantly impaired. The present study further evaluated the mechanisms of these observations by examining the in vivo effect of vincristine on (1) the pancreatic /3-cell microtubular structures and (2) insulin release in response to arginine, an insulin secretogogue other than glucose. In the first series of studies, the pancreases were removed from the rats at 60 and 120 min after vincristine (0.15 mg/kg; i.v.) or vehicle (control) administration for electron microscopy. Morphometric analysis revealed that the number of /3-cell microtubules was similar in the vincristinetreated and the control rats. Furthermore, the mean microtubular length in vincristine-treated rats was also similar to that observed in the control rats. In the next series of studies, at 10, 60, or 120 min after vincristine (0.15 mg/kg; i.v.), insulin levels in response to an i.v. arginine pulse were similar in the vincristinetreated and in the control rats at all time intervals between 2 and 30 min. A parallel study once again demonstrated that glucose-induced insulin release and glucose tolerance were significantly impaired at 120 min after vincristine treatment. These findings indicate that (1) In the intact rat, inhibition of glucose-induced insulin release by vincristine occurs in the absence of any demonstrable changes in the /3-cell microtubular structure; and (2) even though vincristine inhibits glucose-induced insulin release, it has no effect on arginine-induced insulin release. Therefore, in

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Dissociation of the Effects of Vincristine on Stimulated Insulin Release and the Pancreatic β-Cell Microtubular Structures in the Intact Rat

Shah¹,

Stevens²,

Sorensen³

1981

Diabetes

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“…The importance of microtubules in the intracellular transport has been derived from the observations that agents such as colchicine, vinblastine, and vincristine which are known to cause disruption of microtubular structures have been shown to inhibit catecholamine secretion from adrenal medulla (Poisner & Bernstein 1971), iodine secretion from the thyroid gland (Williams & Wolff 1970), pro¬ lactin secretion from the pituitary tumour cells in culture (Gautvik & Tashjian 1973) and insulin release in vitro from perfused pancreas and iso¬ lated perifused islets (Lacy et al 1968;Malaisse et al 1971Malaisse et al , 1975. We have also shown that colchi¬ cine and vincristine cause inhibition of glucoseinduced insulin release in vivo (Shah & Wongsurawat 1978;Shah et al 1979). However, our recent studies (Shah et al 1981(Shah et al , 1982 have shown that in the intact rat: 1) vincristine caused inhibi¬ tion of glucose-induced insulin release in the presence or absence of morphologic disruptions of the beta cell microtubules; and 2) a marked morphological alteration of the beta cell microtubules has failed to inhibit arginine-induced insulin release in the intact rat.…”

mentioning

confidence: 58%

“…For example, colchicine has been shown to affect concanavalin A receptors on white blood cells (Madyastha et al 1977). Dissociation of the effects of vincristine on the beta cell microtubular struc¬ tures and on the stimulated insulin release ob¬ served in our previous studies have shown that the effect of these agents on insulin release is mediated by mechanisms other than microtubular dis¬ ruption (Shah et al 1979(Shah et al , 1981(Shah et al , 1982a(Shah et al , 1982b). …”

Section: Discussionmentioning

confidence: 86%

The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat

Shah

Hurks

Udomphonkul

et al. 1987

Acta Endocrinologica

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The effect of vincristine on immunoreactive parathyroid hormone (iPTH) release and parathyroid cell microtubular structures was evaluated in intact, unanaesthetized, and unrestrained rats with indwelling catheters. In overnight fasted rats, blood samples were collected before and at 30, 60 and 120 min after iv vincristine administration in low dosage (0.15 mg/kg) or in higher dosage (0.5 mg/kg) or vehicle (controls) for serum iPTH and calcium determinations. Mean baseline serum iPTH and calcium concentrations were similar in the vincristine-treated and the control rat. Following the low dose vincristine treatment, serum iPTH slightly but significantly declined to 89 \m=+-\5% at 30 min and remained at this low level at 60 and 120 min as compared to those observed in control rat. Similarly, iPTH concentrations after higher doses of vincristine were also significantly decreased to 87 \m=+-\4% at 30 min and to 83 \m=+-\ 4%at 60 min, and 86 \m=+-\7% at 120 min as compared to those observed in the control rat. Serum calcium concentrations were similar in the vincristine\x=req-\ treated and control rats. In the next study, each of the rats received vincristine and vehicle in a random order, 10 days apart. In this study also, mean serum iPTH significantly declined to 85 \m=+-\7% at 60 and 120 min during vincristine treatment as compared with those observed during the vehicle treatment in the same rats. Parathyroid glands were removed from rats between 60 and 120 min after vincristine or vehicle treatments for electron microscopy. Morphometric analysis revealed that the number of microtubules and mean microtubular length of the parathyroid cells were similar in the vincristine-treated rats to those observed in the control rats. Therefore, 1) in the intact rat, even low dosage of vincristine cause significant inhibition of iPTH release and 2) this inhibition occurs in the absence of any morphological alteration in the parathyroid cell microtubular structures.

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“…3 " 5 We have also shown that vincristine and colchicine inhibit glucose-induced insulin release in vivo. 6 - 7 However, our recent studies 8 - 9 have shown that in the intact rat: (1) vincristine caused inhibition of glucose-induced insulin release in the presence or absence of morphologic disruption of the beta-cell microtubules; but, in contrast, (2) vincristine failed to inhibit arginine-induced insulin release either in the presence or absence of the beta-cell microtubular disruption. These observations suggested that in vivo vincristine may cause inhibition of glucose-induced insulin release by a mechanism other than microtubular disruption.…”

mentioning

confidence: 96%

Glucose but not Arginine Prevents the Inhibitory Effect of Vincristine on Glucose-induced Insulin Release

et al. 1982

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SUMMARYWe have previously shown that in the intact rat: (1) the inhibition of glucose-induced insulin release caused by vincristine occurred in the presence or absence of morphologic disruption of the beta-cell microtubules; and (2) vincristine, however, failed to inhibit arginine-induced insulin release, even in the presence of a marked disruption of the beta-cell microtubules. The present study further evaluated the mechanism of inhibition of vincristine on glucose-induced insulin release in the intact rat. In the first series of studies, glucose (500 mg/kg) was infused over 1 min into fasting rats with indwelling vascular catheters. Five minutes later, vincristine (0.15 mg/kg i.v.) or vehicle (control) was injected. Sixty minutes after vincristine or vehicle treatment, insulin release in response to a 150-mg i.v. glucose pulse was examined. Serum insulin and glucose levels were similar at all time intervals in the vincristine-treated and the control rats. In the next series of studies, the experiments were repeated as above, except arginine (100 mg/kg), instead of glucose, was infused over 1 min before vincristine or vehicle treatment. In these studies, serum insulin in response to a glucose pulse was significantly inhibited in the vincristine-treated rats as compared with control rats. Therefore, in the intact rat, prior exposure to glucose but not arginine protected the beta-cell from the inhibitory effect of vincristine on glucose-induced insulin release. These findings, along with our previous observations, support the concept that arginine-induced insulin release is mediated via mechanisms other than those involved in glucose-induced insulin release and suggest that the in vivo effect of vincristine on glucose-induced insulin release is mediated via alteration of the beta-cell glucose receptors rather than microtubular structures. DIABETES

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The Diphasic Effect of Vincristine on Glucose-Induced Insulin Secretion and Glucose Tolerance in the Intact Rat*

Cited by 8 publications

References 12 publications

Dissociation of the Effects of Vincristine on Stimulated Insulin Release and the Pancreatic β-Cell Microtubular Structures in the Intact Rat

Dissociation of the Effects of Vincristine on Stimulated Insulin Release and the Pancreatic β-Cell Microtubular Structures in the Intact Rat

The effect of vincristine on parathyroid hormone release and on the parathyroid cell microtubular structures in the intact rat

Glucose but not Arginine Prevents the Inhibitory Effect of Vincristine on Glucose-induced Insulin Release

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