212 results match your criteria improved diazoxide


Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents.

Plants (Basel) 2021 Jun 11;10(6). Epub 2021 Jun 11.

School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.

  is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Read More

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Suppression of hyperinsulinemia restores growth hormone secretion and metabolism in obese mice.

J Endocrinol 2021 Jul 12;250(3):105-116. Epub 2021 Jul 12.

School of Biomedical Sciences, University of Queensland, Queensland, Australia.

The well-balanced secretion between insulin and growth hormone (GH) is essential in regulating substrate metabolism, energy metabolism, and body composition. High insulin and low GH levels are often observed in obesity, contributing to reduced energy expenditure and further fat accumulation. Although suppression of hyperinsulinemia is proposed as a treatment for obesity, changes in GH secretion and energy metabolism following this treatment are not thoroughly studied. Read More

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Recent updates in the management of infants and children with hyperinsulinism.

Authors:
Paul S Thornton

Curr Opin Pediatr 2021 08;33(4):424-429

Cook Children's Medical Center, Fort Worth, Texas, USA.

Purpose Of Review: To highlight recent advances in early diagnosis and the changing treatment paradigm for hyperinsulinism (HI) which can result in shorter hospitalizations, higher rates of cure and improved neurological outcome.

Recent Findings: Recent literature has shown that following publication of the pediatric endocrinology society guidelines for diagnosing hypoglycemia there have been higher rates of diagnosis of acquired and genetic HI. Studies of neurological outcome have found that poor outcomes are associated with delay between initial hypoglycemia and instigation of treatment for HI, hypoglycemic seizures and frequency of glucose <20 mg/dL. Read More

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First report on the use of pasireotide in a case of severe congenital hyperinsulinism due to a homozygous ABCC8 mutation.

Ann Pediatr Endocrinol Metab 2021 May 7. Epub 2021 May 7.

Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as second-line treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide while pasireotide, a second-generation somatostatin analogue, may be more effective in reducing insulin secretion. Read More

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Challenges in management of transient hyperinsulinism - a retrospective analysis of 36 severely affected children.

J Pediatr Endocrinol Metab 2021 Jul 16;34(7):867-875. Epub 2021 Apr 16.

Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Objectives: Transient hyperinsulinism (THI) is a hypoglycemia disorder which resolves spontaneously within the first weeks or months of life. The pathomechanism of THI is not elucidated yet; however, it is known that perinatal stress predisposes for THI. We aimed to characterize the clinical phenotype and treatment of children with THI, and to identify options for improved management. Read More

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Insulinotropic and antidiabetic properties of Eucalyptus citriodora leaves and isolation of bioactive phytomolecules.

J Pharm Pharmacol 2021 Jul;73(8):1049-1061

School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.

Objective: The aim of this study was to delineate the mechanisms of action of the plant Eucalyptus citriodora used traditionally for the treatment of type 2 diabetes.

Methods: Insulin secretion and signal transduction were measured using clonal pancreatic β-cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes and in vitro systems assessed additional glucose-lowering actions. Read More

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SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism.

Diabetologia 2021 Mar 6;64(3):630-640. Epub 2021 Jan 6.

Stem Cells and Metabolism Research Program in the Faculty of Medicine of the University of Helsinki, Helsinki, Finland.

Aims/hypothesis: Congenital hyperinsulinism caused by mutations in the K-channel-encoding genes (KHI) is a potentially life-threatening disorder of the pancreatic beta cells. No optimal medical treatment is available for patients with diazoxide-unresponsive diffuse KHI. Therefore, we aimed to create a model of KHI using patient induced pluripotent stem cell (iPSC)-derived islets. Read More

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Anti-hyperglycaemic and insulin-releasing effects of leaves and isolation and characterisation of active compounds.

Br J Nutr 2020 Dec 17:1-15. Epub 2020 Dec 17.

School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, Co. Londonderry, Northern Ireland, UK.

Anti-diabetic actions of Camellia sinensis leaves, used traditionally for type 2 diabetes (T2DM) treatment, have been determined. Insulin release, membrane potential and intra-cellular Ca were studied using the pancreatic β-cell line, BRIN-BD11 and primary mouse pancreatic islets. Cellular glucose-uptake/insulin action by 3T3-L1 adipocytes, starch digestion, glucose diffusion, dipeptidyl peptidase-4 (DPP-IV) activity and glycation were determined together with in vivo studies assessing glucose homoeostasis in high-fat-fed (HFF) rats. Read More

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December 2020

Diazoxide and Exercise Enhance Muscle Contraction during Obesity by Decreasing ROS Levels, Lipid Peroxidation, and Improving Glutathione Redox Status.

Antioxidants (Basel) 2020 Dec 4;9(12). Epub 2020 Dec 4.

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Múgica S/N, Col. Felicitas del Río, Morelia, Michoacán 58030, Mexico.

Obesity causes insulin resistance and hyperinsulinemia which causes skeletal muscle dysfunction resulting in a decrease in contraction force and a reduced capacity to avoid fatigue, which overall, causes an increase in oxidative stress. K channel openers such as diazoxide and the implementation of exercise protocols have been reported to be actively involved in protecting skeletal muscle against metabolic stress; however, the effects of diazoxide and exercise on muscle contraction and oxidative stress during obesity have not been explored. This study aimed to determine the effect of diazoxide in the contraction of skeletal muscle of obese male Wistar rats (35 mg/kg), and with an exercise protocol (five weeks) and the combination from both. Read More

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December 2020

Pulmonary Hypertension Following Increased Dosing of Diazoxide in an Infant.

Int Heart J 2020 Sep 12;61(5):1084-1087. Epub 2020 Sep 12.

Department of Pediatrics, Yamaguchi University Graduate School of Medicine.

Diazoxide, a drug used to treat hyperinsulinemic hypoglycemia (HH), is associated with pulmonary hypertension (PH), as reported by the US Food and Drug Administration. However, no report has detailed the association between diazoxide dose and PH development. We report a case of an infant with HH, subsequently complicated by diazoxide-induced PH. Read More

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September 2020

Congenital hyperinsulinsim: case report and review of literature.

Pan Afr Med J 2020 24;35:53. Epub 2020 Feb 24.

Department of pediatrics, Military Teaching Hospital Mohammed V, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.

Neonatal hypoglycemia (NH) is one of the most common abnormalities encountered in the newborn. Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Read More

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December 2020

Effects of on insulin secretion, dipeptidyl peptidase IV activity and both carbohydrate digestion and absorption indicate potential as an adjunctive therapy for diabetes.

Br J Nutr 2020 11 10;124(10):1021-1034. Epub 2020 Jun 10.

School of Biomedical Sciences, Ulster University, Co. Londonderry, Northern IrelandBT52 1SA, UK.

Spirulina platensis has been found to be useful in the treatment of type 2 diabetes. The present study aims to elucidate the effects of ethanol extract and butanol fraction of S. platensis on insulin release and glucose homoeostasis in type 2 diabetic rats, together with their mechanism of actions. Read More

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November 2020

Diazoxide Preconditioning of Nonhuman Primate Pancreas Improves Islet Isolation Outcomes by Mitochondrial Protection.

Pancreas 2020 May/Jun;49(5):706-713

From the Department of Surgery/Transplant, University of Illinois at Chicago, Chicago, IL.

Objectives: Previously, we showed that diazoxide (DZ), an effective ischemic preconditioning agent, protected rodent pancreas against ischemia-reperfusion injury. Here, we further investigate whether DZ supplementation to University of Wisconsin (UW) solution during pancreas procurement and islet isolation has similar cytoprotection in a preclinical nonhuman primate model.

Methods: Cynomolgus monkey pancreata were flushed with UW or UW + 150 μM DZ during procurement and preserved for 8 hours before islet isolation. Read More

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Rare association of Beckwith-Wiedemann syndrome with Hirschsprung's disease in an infant with hypoglycemia.

BMJ Case Rep 2020 Apr 26;13(4). Epub 2020 Apr 26.

Department of Pediatrics, Jehangir Hospital, Pune, Maharashtra, India.

Hypoglycaemic due to congenital hyperinsulinism in Beckwith-Wiedemann syndrome is commonly seen. It is usually transient and is managed by enteral feeds, high glucose-containing intravenous fluids and medications like diazoxide. We describe a case of an infant with genetically proven Beckwith-Wiedemann syndrome with prolonged hyperinsulinemic hypoglycaemia. Read More

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LONG-TERM EFFECT OF LU-DOTATATE ON SEVERE AND REFRACTORY HYPOGLYCEMIA ASSOCIATED WITH MALIGNANT INSULINOMA.

AACE Clin Case Rep 2019 Nov-Dec;5(6):e330-e333. Epub 2019 Jun 26.

Objective: Malignant insulinoma is an extremely uncommon tumor that is usually accompanied by severe hypoglycemia that is difficult to manage. At this time, the long-term effect of Lu-DOTATATE (lutetium [Lu-177]-DOTA-Tyr3-octreotate) on this tumor is not well known.

Methods: We report a case of severe, life-threatening, and refractory hypoglycemia associated with malignant insulinoma treated with Lu-DOTATATE. Read More

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Refractory Metastatic Insulinoma Treated with Everolimus, Complicated by Cryptogenic Organizing Pneumonia.

Am J Med Case Rep 2019 18;7(7):125-132. Epub 2019 Jun 18.

Department of Medicine and Department of Endocrinology, State University of New York: Downstate Medical Center.

Insulinoma is a rare neuroendocrine pancreatic islet cell tumor of which the majority are benign and solitary. Its estimated incidence is 2 to 4 cases per 1 million person-years. We report the case of an 82-year-old female who presented with metastatic insulinoma to the liver and retroperitoneal lymph nodes. Read More

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Diazoxide Modulates Cardiac Hypertrophy by Targeting H2O2 Generation and Mitochondrial Superoxide Dismutase Activity.

Curr Mol Pharmacol 2020 ;13(1):76-83

Faculdade de Medicina, Universidade Federal do Cariri, Barbalha, CE, Brazil.

Background: Cardiac hypertrophy involves marked wall thickening or chamber enlargement. If sustained, this condition will lead to dysfunctional mitochondria and oxidative stress. Mitochondria have ATP-sensitive K+ channels (mitoKATP) in the inner membrane that modulate the redox status of the cell. Read More

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A rare case of congenital hyperinsulinism (CHI) due to dual genetic aetiology involving HNF4A and ABCC8.

J Pediatr Endocrinol Metab 2019 Mar;32(3):301-304

Department of Paediatric Endocrinology, Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.

Background Congenital hyperinsulinism (CHI) occurs due to an unregulated insulin secretion from the pancreatic β-cells resulting in hypoglycaemia. Causative mutations in multiple genes have been reported. Phenotypic variability exists both within and between different genetic subgroups. Read More

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Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism.

Orphanet J Rare Dis 2018 12 22;13(1):230. Epub 2018 Dec 22.

Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany.

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Read More

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December 2018

The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia.

Horm Res Paediatr 2019 16;91(1):56-61. Epub 2018 Aug 16.

Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom,

Background: A long-acting somatostatin analogue (lanreotide) is used in the management of a diazoxide-unresponsive diffuse form of congenital hyperinsulinism (CHI). However, no reports of its use in patients with the focal form of CHI exist. Case 1: A 1-month-old boy diagnosed with diazoxide-unresponsive CHI due to a paternal heterozygous ABCC8 gene mutation showed partial response to octreotide. Read More

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November 2019

The effect of Diazoxide on norepinephrine-induced cardiac hypertrophy, in vitro.

Authors:
Celal Guven

Cell Mol Biol (Noisy-le-grand) 2018 Jul 30;64(10):50-54. Epub 2018 Jul 30.

The Department of Biophysics, Faculty of Medicine, Nigde Omer Halisdemir University, Nigde, Turkey.

Cardiac hypertrophy is associated with mitochondrial dysfunctions, which leads to heart failure if sustained. The aim of present study is to test hypothesis whether activation of mitochondrial KATP channel (mitoKATP) by diazoxide improve mitochondrial membrane potential (MMP) and oxidative stress in an in vitro model of cardiac hypertrophy. Rat cardiomyocytes cell line (H9c2) was used to create four groups as control, diazoxide, hypertrophy, hypertrophy and diazoxide. Read More

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Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats.

Nutrients 2018 Jul 20;10(7). Epub 2018 Jul 20.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden.

() is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. Read More

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Transgenic overexpression of the SUR2A-55 splice variant in mouse heart reduces infract size and promotes protective mitochondrial function.

Heliyon 2018 Jul 4;4(7):e00677. Epub 2018 Jul 4.

Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.

ATP-sensitive potassium channels found in both the sarcolemma (sarcK) and mitochondria (mitoK) of cardiomyocytes are important mediators of cardioprotection during ischemic heart disease. Sulfonylurea receptor isoforms (SUR2), encoded by , an ATP-binding cassette family member, form regulatory subunits of the sarcK channel and are also thought to regulate mitoK channel activity. A short-form splice variant of SUR2 (SUR2A-55) was previously shown to target mitochondria and display diaxoxide and ATP insensitive K activity when co-expressed with the inward rectifier channels Kir6. Read More

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Flavonoid 8-O-Glucuronides from the Aerial Parts of Malva verticillata and Their Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish.

Molecules 2018 Apr 4;23(4). Epub 2018 Apr 4.

Graduate School of Biotechnology & Department of Oriental Medicine Biotechnology, Kyung-Hee University, Yongin 17104, Korea.

Malva verticillata (Cluster mallow), a leafy vegetable that has been popular in East Asia for a long time, has also been used in herbal teas and medicines. The aqueous fraction of the aerial parts of Malva verticillata, exhibiting a very high quantity of flavonoids compared to the EtOAc and -BuOH fractions, exhibited significant recovery effects on pancreatic islets damaged by alloxan in zebrafish larvae. Thus, the bioactive components responsible for this anti-diabetic activity were investigated. Read More

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Optimized induction of beta common receptor enhances the neuroprotective function of erythropoietin in spinal cord ischemic injury.

J Thorac Cardiovasc Surg 2018 06 9;155(6):2505-2516. Epub 2018 Feb 9.

Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado, Aurora, Colo.

Background: Paraplegia remains the most feared complication of complex thoracoabdominal aortic intervention. Although erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, it does not work until expression of the beta common receptor subunit of the EPO receptor (βcR) is induced by ischemia. We hypothesized that the βcR can be induced by diazoxide (DZ), amplifying the neuroprotective effects of EPO in spinal cord ischemia-reperfusion injury. Read More

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Chronic diazoxide treatment decreases fat mass and improves endurance capacity in an obese mouse model of Prader-Willi syndrome.

Mol Genet Metab 2018 04 27;123(4):511-517. Epub 2018 Feb 27.

Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada. Electronic address:

Excess fat mass is a cardinal feature of Prader-Willi syndrome (PWS) that is recapitulated in the Magel2-null mouse model of this genetic disorder. There is a pressing need for drugs that can prevent or treat obesity in children with PWS. Recently, a clinical study of a controlled release form of the benzothiadiazine derivative diazoxide demonstrated improved metabolic parameters and decreased fat mass in obese children and adults with PWS. Read More

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Mitochondrial ATP-sensitive potassium channel regulates mitochondrial dynamics to participate in neurodegeneration of Parkinson's disease.

Biochim Biophys Acta Mol Basis Dis 2018 Apr 17;1864(4 Pt A):1086-1103. Epub 2018 Jan 17.

Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, PR China. Electronic address:

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. Mitochondrial dysfunction has been the focus of the pathogenesis of PD. The mitochondrial ATP-sensitive potassium channel (mitoKATP) plays a significant role in mitochondrial physiology and has been extensively shown to protect against ischemic and brain reperfusion injury. Read More

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Effect of diazoxide on Friedreich ataxia models.

Hum Mol Genet 2018 03;27(6):992-1001

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy.

Friedreich ataxia (FRDA) is an inherited recessive disorder caused by a deficiency in the mitochondrial protein frataxin. There is currently no effective treatment for FRDA available, especially for neurological deficits. In this study, we tested diazoxide, a drug commonly used as vasodilator in the treatment of acute hypertension, on cellular and animal models of FRDA. Read More

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Eriodictyol stimulates insulin secretion through cAMP/PKA signaling pathway in mice islets.

Eur J Pharmacol 2018 Feb 8;820:245-255. Epub 2017 Dec 8.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Pakistan; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah-21412, Saudi Arabia.

Eriodictyol, a flavonoid isolated from Lyonia ovalifolia, was found to be the most potent insulin secretagogue in our preliminary studies. Here, we explored mechanism(s) of insulin secretory activity of eriodictyol in vitro and in vivo. Mice islets and MIN6 cells were incubated in basal and stimulatory glucose containing eriodictyol with or without agonist/antagonist. Read More

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February 2018

Development of Pulmonary Hypertension During Treatment with Diazoxide: A Case Series and Literature Review.

Pediatr Cardiol 2017 Aug 22;38(6):1247-1250. Epub 2017 Jun 22.

San Antonio Military Medical Center, San Antonio, USA.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. The mainstay of medical management for CHI is diazoxide. Diazoxide inhibits insulin release from the pancreas, but also causes smooth muscle relaxation and fluid retention so it is typically given with chlorothiazide. Read More

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