The use of diazoxide in the management of spontaneous hypoglycemia in patients with ESRD

Mesmar, Bayan; Kristan, Megan; Satyarengga, Medha; Lamos, Elizabeth M.; Malek, Rana; Munir, Kashif M.

doi:10.1007/s13730-020-00471-z

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…We reasoned that the results of GTT obtained from sunitinib-treated rats might be associated with an enhanced glucose-induced insulin secretion and the impaired renal insulin clearance, which may lead to spontaneous hypoglycemia ( Malik et al, 2016 ; Mesmar et al, 2020 ). Therefore, we detected the levels of serum insulin and glucagon under both the fasting and feeding conditions, respectively.…”

Section: Resultsmentioning

confidence: 99%

Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension

et al. 2021

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Antiangiogenic tyrosine kinases inhibitors induce hypertension, which may increase the incidents of cardiovascular complications and limit their use. However, the mechanisms by which usage of TKIs results in hypertension have not been fully understood. Here, we report the potential mechanisms of how sunitinib, a widely used TKI, induces hypertension. Male SD rats were randomly divided into control group and sunitinib-administrated group. We show that sunitinib administration for seven days caused a significant increase in artery blood pressure, along with glycerolipid metabolism abnormalities including decreased food intake and low body weight, hypoglycemia, hyperinsulinemia. Sunitinib administration also resulted in a significant increase in the levels of insulin autoantibody (IAA), cyclic adenosine monophosphate and free fatty acid in serum; whereas, sunitinib administration had no effects on serum glucagon levels. Sunitinib led to the decreased insulin sensitivity as determined by insulin tolerance test (ITT) and glucose tolerance test (GTT), reflecting insulin resistance occurred in sunitinib-treated rats. The results obtained from wire myograph assay in the mesenteric arteries show that endothelium-dependent relaxation, but not endothelium-independent relaxation, was impaired by sunitinib. Furthermore, western blot analysis revealed that the expressions levels of phosphorylated IRS-1, Pellino-1, AKT and eNOS were significantly attenuated by sunitinib in rat mesenteric artery tissues and in the sunitinib-treated primary cultured mesenteric artery endothelial cells. The levels of serum and endothelium-derived nitric oxide were also significantly decreased by sunitinib. Moreover, sunitinib-induced decrease in the expression levels of phosphorylated AKT and eNOS was further reduced by knocking down of Pellino-1 in MAECs. Our results suggest that sunitinib causes vascular dysfunction and hypertension, which are associated with insulin resistance- and Pellino-1-mediated inhibition of AKT/eNOS/NO signaling. Our results may provide a rational for preventing and/or treating sunitinib-induced endothelial dysfunction and hypertension.

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Section: Resultsmentioning

confidence: 99%

Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension

et al. 2021

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All Other Therapeutic Products – Antidotes, Detoxifying Agents (V03), and Contrast Media (V08)

Kutscher¹

2022

Ullmann's Encyclopedia of Industrial Chemistry

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End-stage Renal Disease in Which Diazoxide Was Effective in Treating Hypoglycemia Caused by Late Dumping Syndrome after Gastrectomy

Kato,

Kageyama,

Nakashima

et al. 2024

Intern. Med.

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We herein report a case in which diazoxide was effective in treating reactive hypoglycemia caused by late dumping syndrome in a patient with ESRD. A 50-year-old man with end-stage renal disease (ESRD) and a history of gastrectomy underwent hemodialysis. Although he was administered voglibose to treat recurrent reactive hypoglycemia caused by late dumping syndrome, he had difficulty continuing treatment because of gastrointestinal side effects. When he began diazoxide treatment, the reactive hypoglycemia improved. The dose was gradually increased with no apparent side effects, and the hypoglycemic attacks disappeared one year after the start of treatment.

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The use of diazoxide in the management of spontaneous hypoglycemia in patients with ESRD

Cited by 3 publications

References 21 publications

Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension

Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension

All Other Therapeutic Products – Antidotes, Detoxifying Agents (V03), and Contrast Media (V08)

End-stage Renal Disease in Which Diazoxide Was Effective in Treating Hypoglycemia Caused by Late Dumping Syndrome after Gastrectomy

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