Pancreatic growth and function following surgical treatment of nesidioblastosis in infancy

Schönaü, Eckhard; Deeg, Karl‐Heinz; Huemmer, Hans P.; Akcetin, Y. Z.; Böhles, H.

doi:10.1007/bf02072204

Cited by 27 publications

(10 citation statements)

References 10 publications

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“…Hypoglycemia requiring medical treatment in patients with CHI who underwent pancreatectomy may be explained by the regeneration of the residual pancreatic tissue (36). In our study group, all three patients who had diabetes subsequent to pancreatectomy had homozygous ABCC8 mutations.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics, Management and Long-Term Follow-Up of Turkish Patients with Congenital Hyperinsulinism

Güven¹,

Cebeci²,

Ellard³

et al. 2016

Jcrpe

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Objective:Mutations in the KATP channel genes is the most common cause of congenital hyperinsulinism (CHI) of infancy. Our aim was to report the clinical and genetic characteristics, treatment modalities, and long-term prognosis of patients with CHI.Methods:Clinical and biochemical findings, operation procedures, and results of genetic analysis were retrospectively evaluated in 22 CHI patients from two pediatric endocrine centers in Turkey.Results:Seven of the patients were born large for gestational age. Hypoglycemia was diagnosed within the first 24 hours of life in 9 patients and treatment with diazoxide (n=21) and/or somatostatin (n=8) had been attempted. Seven patients (31.8%) were unresponsive to medical treatment and underwent pancreatectomy. Histological examination of the pancreas confirmed diffuse disease in 6 patients. Diabetes developed in 3 patients following pancreatectomy (10 years, 2.5 years, and immediately after operation). The remaining four patients had neither recurrence of CHI nor of diabetes during the 3.67±0.7 years of follow-up. Sequence analysis identified mutations in 12 out of 19 patients (63%). Mutations in the ABCC8 gene were the most common finding and were found in 6 out of 7 patients who underwent pancreatectomy. Other mutations included a paternally inherited KCNJ11 mutation, a homozygous HADH mutation, and a heterozygous GLUD1 mutation.Conclusion:Mutations in the ABCC8 gene were the most common cause of CHI in our cohort. These mutations were identified in 85% of patients who underwent pancreatectomy. The development of diabetes mellitus after pancreatectomy may occur at any age and these patients should be screened regularly.

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Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics, Management and Long-Term Follow-Up of Turkish Patients with Congenital Hyperinsulinism

Güven¹,

Cebeci²,

Ellard³

et al. 2016

Jcrpe

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“…Recently some studies have reported that hypergastrinemia, induced either medically (e.g., proton pump inhibitor) or surgically (e.g., fundectomy), has a trophic effect on the pancreas after pancreatic resection in animal models. Schonau et al 16 reported that after 95% pancreatectomies in infants with nesidioblastosis, pan- creatic endocrine and exocrine functions were satisfactory and the pancrease showed extensive regrowth. Schlegel et al 15 presented a case that showed complete restoration of the pancreatic volume 1 year after a distal pancreatectomy in a 57-year-old woman diagnosed with mucinous cystadenoma.…”

Section: Discussionmentioning

confidence: 99%

Randomized Prospective Trial of the Effect of Induced Hypergastrinemia on the Prevention of Pancreatic Atrophy After Pancreatoduodenectomy in Humans

Jang

Kim²,

Han³

et al. 2003

Annals of Surgery

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“…The turnover rate was obtained by increasing the glucose concentration in a stepwise manner in the presence of a constant concentration of ATP. The relative activity index is an expression of in situ phosphorylation capacity based on expression at 5 mmol/l of blood glucose and calculated according to the formula previously reported (19).…”

Section: Glucokinase (Gk) Is a Glycolytic Key Enzyme That Functions Amentioning

confidence: 99%

“…Neither subtotal pancreatectomy nor the treatment with diazoxide resolved hypoglycemia of our patient. We can assume that the high turnover and the very low threshold for GSIS induced by GK-Y214C allows high insulin secretion, even with only 5% of the pancreas left, particularly because the infantile pancreas may undergo significant regeneration (19). The absence of response to diazoxide is a characteristic feature shared by some patients with severe familial hyperinsulinism due to mutations in the K ATP channel that are often completely unresponsive to diazoxide.…”

Section: Glucokinase (Gk) Is a Glycolytic Key Enzyme That Functions Amentioning

confidence: 99%

Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation

Cuesta-Muñoz¹,

Huopio²,

et al. 2004

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Glucokinase (GK) is a glycolytic key enzyme that functions as a glucose sensor in the pancreatic ␤-cell, where it governs glucose-stimulated insulin secretion (GSIS). Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturityonset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia. We describe the first case of severe persistent hyperinsulinemic hypoglycemia due to a "de novo" mutation in GCK (Y214C). A baby girl presented with hypoglycemic seizures since the first postnatal day as well as with inappropriate hyperinsulinemia. Severe hypoglycemia persisted even after treatment with diazoxide and subtotal pancreatectomy, leading to irreversible brain damage. Pancreatic histology revealed abnormally large and hyperfunctional islets. The mutation is located in the putative allosteric activator domain of the protein. Functional studies of purified recombinant glutathionyl Stransferase fusion protein of GK-Y214C showed a sixfold increase in its affinity for glucose, a lowered cooperativity, and increased k cat . The relative activity index of GK-Y214C was 130, and the threshold for GSIS predicted by mathematical modeling was 0.8 mmol/l, compared with 5 mmol/l in the wild-type enzyme. In conclusion, we have identified a de novo GCK activating mutation that causes hyperinsulinemic hypoglycemia of exceptional severity. These findings demonstrate that the range of the clinical phenotype caused by GCK mutations varies from complete insulin deficiency to extreme hyperinsulinemia. Diabetes

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Pancreatic growth and function following surgical treatment of nesidioblastosis in infancy

Cited by 27 publications

References 10 publications

Clinical and Genetic Characteristics, Management and Long-Term Follow-Up of Turkish Patients with Congenital Hyperinsulinism

Clinical and Genetic Characteristics, Management and Long-Term Follow-Up of Turkish Patients with Congenital Hyperinsulinism

Randomized Prospective Trial of the Effect of Induced Hypergastrinemia on the Prevention of Pancreatic Atrophy After Pancreatoduodenectomy in Humans

Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation

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