• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.116-120
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• 2016

Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively. We report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth, because of hypoglycemia. Investigations revealed hypoglycemia with hyperinsulinemia, but no ketone bodies, and a low level of free fatty acids. High dose glucose infusion, enteral feeding, and medications could not maintain the patient's serum glucose level. Genetic testing revealed a new variation of ABCC8 mutation. Therefore, we report this case of CHI caused by a novel mutation of ABCC8 in a half-Korean newborn infant with diazoxide-unresponsive hyperinsulinemic hypoglycemia.

• BMB Reports
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• v.43 no.4
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• pp.245-249
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• 2010

GDH has been known to be related with hyperinsulinism-hyperammonemia syndrome. We have screened new drugs with a view to developing effective drugs modulating GDH activity. In the present work, we investigated the effects of a new drug, KHG26377 on glutamate formation and GDH activity in cultured rat islets. When KHG26377 was added to the culture medium for 24 h prior to kinetic analysis, the $V_{max}$ of GDH was decreased by 59% whereas $K_m$ is not significantly changed. The concentration of glutamate decreased by 50% and perfusion of islets with KHG26377 reduced insulin release by up to 55%. Our results show that KHG26377 regulates insulin release by inhibiting GDH activity in primary cultured islets and support the previous studies for the connection between GDH activity and insulin release. Further studies are required to determine in vivo effects and pharmacokinetics of the drug.

• Advances in pediatric surgery
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• v.1 no.2
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• pp.195-199
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• 1995

Nesidioblastosis in one of the causes of hyperinsulinemic hypoglysemia in infancy. The most important goal of treatment for persistent hypoglycemia is the prevention of permanent brain damage. The early surgical management is satisfactory to this goal in nesidioblastosis and maintains normal blood sugar level without administration of drugs or supplement of sugar postoperatively in many cases. We experienced a female infant of 3 months old who has suffered from persistent hypoglysemia due to hyperinsulinism and was suspected nesidioblastosis for its cause clinically. She underwent 95% distal pancreatectomy. The histologic findings of nesidioblastosis was confirmed postoperatively. No postoperative complication was occured and her blood sugar levels were maintained within normal range without medical treatment.

• Journal of Veterinary Science
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• v.24 no.3
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• pp.39.1-39.6
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• 2023

A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 µIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule. Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulininduced hypoglycemia in dogs.

• BMB Reports
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• v.45 no.8
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• pp.458-463
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• 2012

We investigated the mechanisms involved in KHG26377 regulation of glutamate dehydrogenase (GDH) activity, focusing on the roles of SIRT4 and SIRT3. Intraperitoneal injection of mice with KHG26377 reduced GDH activity with concomitant repression of glucose-induced insulin secretion. Consistent with their known functions, SIRT4 ribosylated GDH and reduced its activity, and SIRT3 deacetylated GDH, increasing its activity. However, KHG26377 did not affect SIRT4-mediated ADP-ribosylation/inhibition or SIRT3-mediated deacetylation/activation of GDH. KHG26377 had no effect on SIRT4 protein levels, and did not alter total GDH, acetylated GDH, or SIRT3 protein levels in pancreatic mitochondrial lysates. These results suggest that the mechanism by which KHG26377 inhibits GDH activity and insulin secretion does not involve ADP-ribosylation of GDH by SIRT4 or deacetylation of GDH by SIRT3.

• Korean Journal of Veterinary Research
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• v.49 no.4
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• pp.365-368
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• 2009

A six-year-old female cocker spaniel presented with recurring episodes of pelvic limb weakness and intermittent seizures. Laboratory analysis revealed marked hypoglycemia and an elevated serum insulin concentration. A pancreatic beta-cell tumor at stage III ($T_1N_1M_1$) was diagnosed based on serial blood glucose and insulin measurements along with diagnostic imaging. The patient survived for 140 days after diagnosis with medical management, including frequent feeding and prednisolone therapy. On necropsy, necrosis and masses in the peripancreatic omentum and liver were found; pancreatic beta-cell neoplasia with metastasis to the liver was confirmed by histopathologic examination. This case reports hyper-insulinism in a dog presenting with hypoglycemic seizures.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.4
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• pp.251-258
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• 2016

Purpose: This study aimed to evaluate the utility of acanthosis nigricans (AN) severity as an index for predicting insulin resistance in obese children. Methods: The subjects comprised 74 obese pediatric patients who attended the Department of Pediatrics at Chosun University Hospital between January 2013 and March 2016. Waist circumference; body mass index; blood pressure; fasting glucose and fasting insulin levels; lipid profile; aspartate transaminase, alanine transaminase, glycated hemoglobin, C-peptide, and uric acid levels; and homeostatic model assessment insulin resistance (HOMA-IR) and quantitative insulin check sensitivity index (QUICKI) scores were compared between subjects with AN and those without AN. Receiver operating characteristic curves were used to investigate the utility of the AN score in predicting insulin resistance. HOMA-IR and QUICKI were compared according to AN severity. Results: The With AN group had higher fasting insulin levels ($24.1{\pm}21.0\;mU/L$ vs. $9.8{\pm}3.6\;mU/L$, p<0.001) and HOMA-IR score ($5.74{\pm}4.71$ vs. $2.14{\pm}0.86$, p<0.001) than the Without AN group. The AN score used to predict insulin resistance was 3 points or more (sensitivity 56.8%, specificity 83.9%). HOMA-IR scores increased with AN severity, from the Without AN group (mean, 2.15; 95% confidence interval [CI], 1.72-2.57) to the Mild AN (mean, 4.15; 95% CI, 3.04-5.25) and Severe AN groups (mean, 7.22; 95% CI, 5.08-9.35; p<0.001). Conclusion: Insulin resistance worsens with increasing AN severity, and patients with Severe AN (AN score ${\geq}3$) are at increased risk of insulin resistance.

• Genomics & Informatics
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• v.12 no.4
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• pp.283-288
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• 2014

Among all serious diseases globally, diabetes (type 1 and type 2) still poses a major challenge to the world population. Several target proteins have been identified, and the etiology causing diabetes has been reasonably well studied. But, there is still a gap in deciding on the choice of a drug, especially when the target is mutated. Mutations in the KCNJ11 gene, encoding the kir6.2 channel, are reported to be associated with congenital hyperinsulinism, having a major impact in causing type 1 diabetes, and due to the lack of its 3D structure, an attempt has been made to predict the structure of kir6.2, applying fold recognition methods. The current work is intended to investigate the affinity of four phytochemicals namely, curcumin (Curcuma longa), genistein (Genista tinctoria), piperine (Piper nigrum), and pterostilbene (Vitis vinifera) in a normal as well as in a mutant kir6.2 model by adopting a molecular docking methodology. The phytochemicals were docked in both wild and mutated kir6.2 models in two rounds: blind docking followed by ATP-binding pocket-specific docking. From the binding pockets, the common interacting amino acid residues participating strongly within the binding pocket were identified and compared. From the study, we conclude that these phytochemicals have strong affinity in both the normal and mutant kir6.2 model. This work would be helpful for further study of the phytochemicals above for the treatment of type 1 diabetes by targeting the kir6.2 channel.