Direct diabetogenic effect of diltiazem ?

Iversen, E; Jeppesen, Dorthe Lisbeth; Steensgaard-Hansen, Frank

doi:10.1111/j.1365-2796.1990.tb00160.x

Cited by 6 publications

(6 citation statements)

References 11 publications

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“…Calcium channel antagonists have been associated with the development of diabetes, impaired glucose tolerance and insulin resistance, presumably through blocking calcium induced insulin secretion [27][28][29]. However, studies suggest that at hemodynamically active doses, calcium antagonists do not normally interfere with insulin release nor impair glucose tolerance in man.…”

Section: Discussionmentioning

confidence: 99%

Direct Vasodepressor Effects of Pioglitazone in Spontaneously Hypertensive Rats

et al. 1998

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Effects of pioglitazone on plasma insulin levels, systolic blood pressure and arterial reactivity were studied in spontaneously hypertensive (SH) rats. Chronic treatment of SH rats with pioglitazone decreased plasma insulin levels and blood pressure. Direct effects of pioglitazone on vascular reactivity were also studied in aortae and superior mesenteric arteries from SH rats. Pioglitazone markedly inhibited arginine vasopressin (AVP) and norepinephrine (NE) responses without affecting responses to potassium chloride (KCl). These data suggest that (a) antihypertensive effects of pioglitazone in SH rats may be mediated via a direct vasodepressor effect, and (b) vasodilation may be coupled to insulin sensitivity in SH rats.

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Section: Discussionmentioning

confidence: 99%

Direct Vasodepressor Effects of Pioglitazone in Spontaneously Hypertensive Rats

et al. 1998

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“…Calcium channel antagonists are reportedly associated with the development of diabetes, impaired glucose tolerance, and insulin resistance (6)(7)(8)20,21). However, a large body of evidence also suggests that calcium antagonists do not alter glucose handling in nondiabetic and diabetic subjects (5,22).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in cases where it is suggested that calcium antagonists cause either insulin resistance or impaired glucose tolerance, it will be important to deter-mine if the calcium antagonists are being displaced from the plasma-binding proteins. If subsequent clinical studies demonstrate that treatment of some individuals with calcium antagonists, either alone or in combination with other drugs, causes either insulin resistance (8), impaired glucose tolerance (21,22), or diabetes (6,7), then this study may play a role in the initiation of additional biochemical studies of the action of calcium antagonists on insulin-mediated responses in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

“…Calcium antagonists also are used to treat individuals with non-insulin-dependent diabetes mellitus (NIDDM), mainly because calcium antagonists have an insignificant effect on carbohydrate metabolism in vivo (2)(3)(4)(5). However, in some cases, calcium antagonists are reported to cause diabetes mellitus (6,7) or insulin resistance (8). Therefore, we investigated whether calcium antagonists have direct effects on glucose metabolism in skeletal muscle, which is the major site for insulinmediated glucose disposal in rats and humans (9,10).…”

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confidence: 99%

“…The calcium antagonists verapamil (a phenylalkamine), diltiazem (a benzothiazepine), and nifedipine (a dihydropyridine) were used. We used these three drugs because studies examining alteration in glucose tolerance in humans have normally used nifedipine or verapamil or diltiazem (2)(3)(4)(5)(6)(7). Caution is important with regard to extrapolating effects observed in skeletal muscle preparations in vitro to skeletal muscle in vivo.…”

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confidence: 99%

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Effects of Calcium Antagonists on Insulin-Mediated Glucose Metabolism in Skeletal Muscle

Foot

Leighton²

1994

Diabetes

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The effect of three calcium antagonists (verapamil, diltiazem, and nifedipine) on insulin effects was investigated in isolated rat soleus muscles. Soleus muscles were incubated in the presence of insulin (100 microU/ml), a concentration that stimulates the rates of lactate formation and glycogen synthesis half-maximally and with and without a calcium antagonist. A decrease (48%; P < 0.001) was noted in the insulin-mediated rate of glycogen synthesis by verapamil at 100 microM; no effect was observed at lower concentrations of verapamil. Diltiazem decreased the insulin-mediated rates of glycogen synthesis by 36 (P < 0.001), 64 (P < 0.001), and 73% (P < 0.001) at 1, 10, and 100 microM, respectively. Nifedipine decreased the insulin-mediated rates of glycogen synthesis by 37% at 0.1 microM (P < 0.001), 36% at 1 microM (P < 0.001), 21% at 10 microM (P < 0.05), and 72% at 100 microM (P < 0.001). Verapamil at 100 microM decreased lactate formation by 48% (P < 0.001). However, diltiazem increased the rate of lactate formation by 22 (P < 0.01), 43 (P < 0.001), and 61% (P < 0.001) at 1, 10, and 100 microM, respectively. In contrast, nifedipine increased the insulin-mediated rate of lactate formation by 45% only at 100 microM (P < 0.01). The increased rate of lactate formation was probably caused by an increased rate of glycogenolysis, because high concentrations of all the calcium antagonists significantly decreased muscle glycogen content. The insulin-stimulated rate of 3-O-methyl-D-glucose transport or cAMP content was not affected by diltiazem at 1 or 10 microM. The results suggest that the calcium antagonists work by a mechanism, possibly by activating a calcium channel or an extracellular receptor, to influence markedly insulin-mediated intracellular glucose metabolism in skeletal muscle.

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