Drug therapy in leucine-sensitive hypoglycemia

Drash, Allan L.; Wolff, Frederick W.

doi:10.1016/0026-0495(64)90133-7

Cited by 105 publications

(30 citation statements)

References 2 publications

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“…Drash and Wolff (29) first reported its use in a leucine-sensitive child with idiopathic hypoglycemia. In two patients with metastatic islet cell carcinoma, Bleicher, Chowdhury, and Goldner (12) and Ernesti, Mitchell, Raben, and Gilboa (13) were able to prevent frequent severe hypoglycemic attacks by the combined oral administration of diazoxide and other benzothiadiazines.…”

Section: Healthy Subjectsmentioning

confidence: 99%

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Fajans¹,

Floyd²,

Knopf³

et al. 1966

J. Clin. Invest.

152

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Section: Healthy Subjectsmentioning

confidence: 99%

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Fajans¹,

Floyd²,

Knopf³

et al. 1966

J. Clin. Invest.

152

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“…Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.glucose; insulin; glucagon; epinephrine; norepinephrine; adenosine 5Ј-triphosphate-dependent potassium channel DIAZOXIDE IS AN ATP-dependent potassium (K ATP ) channel agonist that is used clinically to treat hyperinsulinemic hypoglycemia (2,8,10,11,13,21,25,34). It opens potassium channels and hyperpolarizes plasma membranes, including those of pancreatic ␤-cells and thus decreases insulin secretion (1,2,6,7,8,10,11,13,21,23,25,34).…”

mentioning

confidence: 99%

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the K_ATPchannel agonist diazoxide

Raju¹,

Cryer²

2005

American Journal of Physiology-Endocrinology and Metabolism

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Raju, Bharathi, and Philip E. Cryer. Mechanism, temporal patterns, and magnitudes of the metabolic responses to the KATP channel agonist diazoxide. Am J Physiol Endocrinol Metab 288: E80 -E85, 2005. First published August 31, 2004; doi:10.1152/ ajpendo.00188.2004.-To assess the mechanism, temporal patterns, and magnitudes of the metabolic responses to the ATP-dependent potassium channel agonist diazoxide, neuroendocrine and metabolic responses to intravenous diazoxide (saline, 1.0 and 2.0 mg/kg) and oral diazoxide (placebo, 4.0 and 6.0 mg/kg) were assessed in healthy young adults. Intravenous diazoxide produced rapid, but transient, decrements (P ϭ 0.0023) in plasma insulin (e.g., nadirs of 2.8 Ϯ 0.5 and 1.8 Ϯ 0.3 U/ml compared with 7.0 Ϯ 1.0 U/ml after saline at 4.0 -7.5 min) and C-peptide (P ϭ 0.0228) associated with dose-related increments in plasma glucose (P ϭ 0.0044) and serum nonesterified fatty acids (P Ͻ 0.0001). After oral diazoxide, plasma insulin appeared to decline, as did C-peptide, again associated with dose-related increments in plasma glucose (P Ͻ 0.0001) and serum nonesterified fatty acids (P ϭ 0.0141). Plasma glucagon, as well as cortisol and growth hormone, was not altered. Plasma epinephrine increased (P ϭ 0.0215) slightly only after intravenous diazoxide. There were doserelated increments in plasma norepinephrine (P ϭ 0.0038 and P ϭ 0.0005, respectively), undoubtedly reflecting a compensatory sympathetic neural response to vasodilation produced by diazoxide, but these would not raise plasma glucose or serum nonesterified fatty acid levels. Thus selective suppression of insulin secretion, without stimulation of glucagon secretion, raised plasma glucose and serum nonesterified fatty acid concentrations. These findings define the temporal patterns and magnitudes of the metabolic responses to diazoxide and underscore the primacy of regulated insulin secretion in the physiological regulation of postabsorptive carbohydrate and lipid metabolism.glucose; insulin; glucagon; epinephrine; norepinephrine; adenosine 5Ј-triphosphate-dependent potassium channel DIAZOXIDE IS AN ATP-dependent potassium (K ATP ) channel agonist that is used clinically to treat hyperinsulinemic hypoglycemia (2,8,10,11,13,21,25,34). It opens potassium channels and hyperpolarizes plasma membranes, including those of pancreatic ␤-cells and thus decreases insulin secretion (1,2,6,7,8,10,11,13,21,23,25,34). However, diazoxide is a nonselective K ATP channel agonist (6, 23), K ATP channels are expressed widely (1, 6, 7), and alternative mechanisms of its plasma glucose-raising action have been proposed (10, 11). One example of the widespread actions of diazoxide is its vasodilating effect (3,22). Indeed, the drug has been used clinically for the urgent treatment of hypertension (3,22). After rapid intravenous injection, the onset of the effect to reduce vascular resistance is rapid (minutes) but, because the drug is Ͼ90% protein bound, prolonged (hours). Despite the initial studies in humans decades ago (8,10,11,21) and the use of...

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“…Drash and Wolf in 1965 used diazoxide successfully to control hypoglycaemia [14]. The terminology, nesidioblastosis was replaced by idiopathic hypoglycaemia of infancy in 1970's.…”

Section: Deficiency Of Counter-regulatory Hormonesmentioning

confidence: 99%

Genetic Disorders Leading to Hypoglycaemia

Suresh¹,

Yap²,

Hussain³

2013

J Genet Syndr Gene Ther

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Hypoglycaemia is common in clinical practice and can be a manifestation of many underlying conditions. It is a biochemical finding and not a diagnosis. Therefore an understanding of the molecular mechanisms that lead to hypoglycaemia is important. At a genetic level, hypoglycaemia can be due to many different genetic disorders both metabolic and endocrine. Some of these genetic disorders present with severe and profound hypoglycaemia in the newborn period yet others can be mild and subtle. Recent advances in the fields of genomics and molecular biology have begun to give fundamental novel insights into the mechanisms regulating blood glucose levels. This state of the art review article will provide an in-depth knowledge into the genetic mechanisms that lead to hypoglycaemia.

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Drug therapy in leucine-sensitive hypoglycemia

Cited by 105 publications

References 2 publications

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the K_ATPchannel agonist diazoxide

Genetic Disorders Leading to Hypoglycaemia

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Drug therapy in leucine-sensitive hypoglycemia

Cited by 105 publications

References 2 publications

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Benzothiadiazine suppression of insulin release from normal and abnormal islet tissue in man.

Mechanism, temporal patterns, and magnitudes of the metabolic responses to the KATPchannel agonist diazoxide

Genetic Disorders Leading to Hypoglycaemia

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Mechanism, temporal patterns, and magnitudes of the metabolic responses to the K_ATPchannel agonist diazoxide