1.Identification of Maturity-Onset Diabetes of the Young Caused by Glucokinase Mutations Detected Using Whole-Exome Sequencing.
Eun Hee CHO ; Jae Woong MIN ; Sun Shim CHOI ; Hoon Sung CHOI ; Sang Wook KIM
Endocrinology and Metabolism 2017;32(2):296-301
Glucokinase maturity-onset diabetes of the young (GCK-MODY) represents a distinct subgroup of MODY that does not require hyperglycemia-lowering treatment and has very few diabetes-related complications. Three patients from two families who presented with clinical signs of GCK-MODY were evaluated. Whole-exome sequencing was performed and the effects of the identified mutations were assessed using bioinformatics tools, such as PolyPhen-2, SIFT, and in silico modeling. We identified two mutations: p.Leu30Pro and p.Ser383Leu. In silico analyses predicted that these mutations result in structural conformational changes, protein destabilization, and thermal instability. Our findings may inform future GCK-MODY diagnosis; furthermore, the two mutations detected in two Korean families with GCK-MODY improve our understanding of the genetic basis of the disease.
Computational Biology
;
Computer Simulation
;
Diabetes Complications
;
Diabetes Mellitus, Type 2*
;
Diagnosis
;
Glucokinase*
;
Humans
2.A Case of Persistent Hyperinsulinemic Hypoglycemia Treated with Diazoxide.
Min Sun KIM ; Eun Hye PARK ; Sun Young KIM ; Dae Yeol LEE
Journal of Korean Society of Pediatric Endocrinology 2007;12(2):164-167
Congenital hyperinsulinism (CHI), the most important cause of hyperglycemia in early infancy, is a heterogenous disease characterized by dysregulation of insulin secretion. Mutations in five proteins have been associated with CHI: sulfonyl urea receptor 1; Kir 6.2; glucokinase; glutamate dehydrogenase and mitochondrial enzyme short-chain 3-hydroxyacyl-coenzyme A dehydrogenase. Early recognition of hypoglycemia, diagnosis of CHI and appropriate management of the hypoglycemia are of the utmost importance to prevent neurologic damage. We report a case of persistent hyperinsulinemic hypoglycemia in 8-month-old male infant. This patient has no mutation in previously mentioned genes. Treatment with diazoxide was successful without any severe side effects in this patient.
Congenital Hyperinsulinism*
;
Diagnosis
;
Diazoxide*
;
Glucokinase
;
Glutamate Dehydrogenase
;
Humans
;
Hyperglycemia
;
Hyperinsulinism
;
Hypoglycemia
;
Infant
;
Insulin
;
Male
;
Oxidoreductases
;
Urea
3.Research development of Mendelian inherited diabetes.
Yan-li YANG ; Yan MENG ; Fu-de FANG
Acta Academiae Medicinae Sinicae 2005;27(3):382-387
Diabetes mellitus is a chronic syndrome of abnormal metabolism, determined by interaction of multifactorial genetic and environmental factors. Some specific types of diabetes, such as MODY, Leprechaunism, lipoatrophic diabetes, and Rabson-Mendenhall syndrome, are monogenic forms of diabetes and are inherited as a Mendelian pattern. The article reviews the research development of these Mendelian inherited diabetes will be reviewed.
Diabetes Mellitus, Type 2
;
etiology
;
genetics
;
Genetic Predisposition to Disease
;
Glucokinase
;
genetics
;
Humans
;
Mutation
;
genetics
4.A novel mutation W257R in gene discovered from a Chinese patient with maturity onset diabetes of the young.
Pingping HONG ; Bingjie GUO ; Li LIN ; Xihua LIN ; Jiaqiang ZHOU
Journal of Zhejiang University. Medical sciences 2019;48(2):200-203
Maturity onset diabetes of the young (MODY) is a monogenic autosomal dominant inherited disease. Its clinical manifestations are asymptomatic with slightly elevated fasting blood glucose and few complications. This paper reports a novel mutation W257R in glucokinase () gene from a Chinese patient with MODY. Heterozygous mutation c.769T>C (p.W257R) in exon 7 of gene (Chr744187343) was found in the proband, her father and brother. This W257R mutation was first reported in Chinese population.
China
;
Diabetes Mellitus, Type 2
;
genetics
;
Female
;
Glucokinase
;
genetics
;
Humans
;
Male
;
Mutation
;
Pedigree
5.MODY Syndrome.
Journal of Korean Society of Pediatric Endocrinology 2010;15(1):1-6
Maturity-onset diabetes of the young (MODY) is a heterogenous form of diabetes characterized by the early onset of diabetes, autosomal dominant inheritance, and impaired insulin secretion. MODY is mostly caused by mutations of the hepatocyte nuclear factor 1-alpha (HNF1-alpha) and glucokinase genes in Caucasians. However most Korean, Japanese, and Chinese patients with MODY do not express known MODY genes. The cause of MODY in Asians has not yet been elucidated clearly. This review focuses on studies on Asian patients with MODY.
Asian Continental Ancestry Group
;
Diabetes Mellitus, Type 2
;
Glucokinase
;
Hepatocyte Nuclear Factor 1-alpha
;
Humans
;
Insulin
;
Wills
6.Effects of medicinal herb water extracts on expression of hepatic glucokinase, pyruvate dehydrogenase and acetyl-CoA carboxylase mRNA.
Hyun Sook KIM ; Tae Woo KIM ; Dae Jung KIM ; Jae Sung LEE ; Myeon CHOE
The Korean Journal of Nutrition 2013;46(2):119-125
We studied the anti-diabetic effects of medicinal herb water extracts on expression of hepatic glucokinase (GCK), pyruvate dehydrogenase (PDH), and acetyl-CoA carboxylase (ACC) mRNA. The medicinal herbs used for experiments were Cornus officinalis (CO), Paeonia suffruticosa Andrews (PSA), Discorea japonica Thunb. (DJ), Rehmannia glutinosa (RG), Lycium chinense (LC), and Pyrus pyrifolia (PP). For GCK mRNA expression, CO, RG, and LC water extracts exhibited a more effective activity than other extracts. Cells treated with RG and LC water extracts showed an increase in expression of PDH mRNA to 191% and 124%, respectively, compared to control. Expression of ACC mRNA was significantly higher in LC water extract. These data indicate that CO, RG, and LC water extracts stimulates expression of hepatic GCK, PDH, and ACC mRNA.
Acetyl Coenzyme A
;
Acetyl-CoA Carboxylase
;
Cornus
;
Glucokinase
;
Lycium
;
Oxidoreductases
;
Paeonia
;
Plants, Medicinal
;
Pyrus
;
Pyruvic Acid
;
Rehmannia
;
RNA, Messenger
;
Water
7.Sargassum coreanum extract alleviates hyperglycemia and improves insulin resistance in db/db diabetic mice.
Mi Hwa PARK ; Young Hwa NAM ; Ji Sook HAN
Nutrition Research and Practice 2015;9(5):472-479
BACKGROUND/OBJECTIVES: The goal of this study was to examine the effect of Sargassum coreanum extract (SCE) on blood glucose concentration and insulin resistance in C57BL-KsJ-db/db mice. MATERIALS/METHODS: For 6 weeks, male C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone (0.005%, w/w). RESULTS: A supplement of the SCE for 6 weeks induced a significant reduction in blood glucose and glycosylated hemoglobin concentrations, and it improved hyperinsulinemia compared to the diabetic control db/db mice. The glucokinase activity in the hepatic glucose metabolism increased in the SCE-supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities in the SCE-supplemented db/db mice were significantly lower than those in the diabetic control db/db mice. The homeostatic index of insulin resistance was lower in the SCE-supplemented db/db mice than in the diabetic control db/db mice. CONCLUSIONS: These results suggest that a supplement of the SCE lowers the blood glucose concentration by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.
Animals
;
Blood Glucose
;
Glucokinase
;
Glucose
;
Glucose-6-Phosphatase
;
Hemoglobin A, Glycosylated
;
Humans
;
Hyperglycemia*
;
Hyperinsulinism
;
Insulin Resistance*
;
Insulin*
;
Male
;
Metabolism
;
Mice*
;
Phosphoenolpyruvate
;
Sargassum*
8.The variation of pancreatic beta-cell specific glucokinase gene promoter at the position of -30 bp in Koreans with gestational diabetes mellitus.
Jin Woo KIM ; In Myung YANG ; Sung Woon KIM ; Young Seol KIM ; Young Kil CHOI ; Jung Taek WOO ; Se Yoon KIM ; Seung Joon OH ; Jeon Ryung PAENG ; Hak Chul CHANG
Korean Journal of Medicine 1999;57(5):916-924
Glucokinase is expressed only in both liver and pancreatic beta cells and has a key role in the regulation of glucose metabolism in these tissues. A number of gene defects associated with glucokinase gene and the cause of non-insulin-dependent diabetes mellitus are known, and the defects along the -30bp promoter site in particular are thought to be related to diabetes and glucose intolerance. To research on gene study related to diabetes, we looked into the relationship between the variation at -30bp of pancreatic beta cell specific glucokinase gene promoter and gestational diabetes mellitus(GDM) in Korea. METHODS: Forty patients with GDM and 62 normal controls were studied. Genomic DNA was extracted from peripheral leukocyte of patients with GDM and normal controls. The nucleotide variation at -30 bp of pancreatic beta cell specific glucokinase gene promoter was analyzed by PCR-SSCP methods. The sequences of amplified DNA were confirmed with direct sequencing method. The clinical features and the response of insulin secretion to oral glucose were analyzed between patients with GDM according to genotypes. RESULTS: Allelic frequency of position -30 bp of pancreatic beta cell specific glucokinase gene promoter did not differ between patients with GDM and normal subjects. However the frequency of G/A and A/A genotypes seemed to show a higher tendency in patients with GDM compare to the normal subjects. Clinical features, insulin response to oral glucose did not differ according to the type of variation at -30bp of pancreatic beta cell specific glucokinase gene promoter. CONCLUSION: These data suggested that the variation at -30 bp of pancreatic beta cell specific glucokinase gene promoter in patients with GDM are unlikely to be one of the possibilities of the genetic factors in the development of GDM. Therefore more sophisticated studies will be needed to elucidate the role of variation at -30bp of pancreatic beta cell specific glucokinase gene promoter in the insulin secretion to oral glucose.
Diabetes Mellitus, Type 2
;
Diabetes, Gestational*
;
DNA
;
Female
;
Genotype
;
Glucokinase*
;
Glucose
;
Glucose Intolerance
;
Humans
;
Insulin
;
Insulin-Secreting Cells
;
Korea
;
Leukocytes
;
Liver
;
Metabolism
;
Pregnancy
9.The variation of pancreatic beta-cell specific glucokinase gene promoter at the position of -30 bp in Koreans with gestational diabetes mellitus.
Jin Woo KIM ; In Myung YANG ; Sung Woon KIM ; Young Seol KIM ; Young Kil CHOI ; Jung Taek WOO ; Se Yoon KIM ; Seung Joon OH ; Jeon Ryung PAENG ; Hak Chul CHANG
Korean Journal of Medicine 1999;57(5):916-924
Glucokinase is expressed only in both liver and pancreatic beta cells and has a key role in the regulation of glucose metabolism in these tissues. A number of gene defects associated with glucokinase gene and the cause of non-insulin-dependent diabetes mellitus are known, and the defects along the -30bp promoter site in particular are thought to be related to diabetes and glucose intolerance. To research on gene study related to diabetes, we looked into the relationship between the variation at -30bp of pancreatic beta cell specific glucokinase gene promoter and gestational diabetes mellitus(GDM) in Korea. METHODS: Forty patients with GDM and 62 normal controls were studied. Genomic DNA was extracted from peripheral leukocyte of patients with GDM and normal controls. The nucleotide variation at -30 bp of pancreatic beta cell specific glucokinase gene promoter was analyzed by PCR-SSCP methods. The sequences of amplified DNA were confirmed with direct sequencing method. The clinical features and the response of insulin secretion to oral glucose were analyzed between patients with GDM according to genotypes. RESULTS: Allelic frequency of position -30 bp of pancreatic beta cell specific glucokinase gene promoter did not differ between patients with GDM and normal subjects. However the frequency of G/A and A/A genotypes seemed to show a higher tendency in patients with GDM compare to the normal subjects. Clinical features, insulin response to oral glucose did not differ according to the type of variation at -30bp of pancreatic beta cell specific glucokinase gene promoter. CONCLUSION: These data suggested that the variation at -30 bp of pancreatic beta cell specific glucokinase gene promoter in patients with GDM are unlikely to be one of the possibilities of the genetic factors in the development of GDM. Therefore more sophisticated studies will be needed to elucidate the role of variation at -30bp of pancreatic beta cell specific glucokinase gene promoter in the insulin secretion to oral glucose.
Diabetes Mellitus, Type 2
;
Diabetes, Gestational*
;
DNA
;
Female
;
Genotype
;
Glucokinase*
;
Glucose
;
Glucose Intolerance
;
Humans
;
Insulin
;
Insulin-Secreting Cells
;
Korea
;
Leukocytes
;
Liver
;
Metabolism
;
Pregnancy
10.Hypoglycemic effect of Rehmannie Radix Preparata (Sookjihwang) extract in streptozotocin-induced diabetic rats.
Shin Jyung KANG ; Cun Liu BAO ; Soojin PARK ; Ae Jung KIM
Nutrition Research and Practice 2010;4(5):438-442
Rhemannie Radix Preparata (RRP) has been previously employed in traditional oriental medicine as a treatment for diabetic thirst and improving blood flow. The aim of this study was to evaluate its hypoglycemic control by assaying the activities of key enzymes of carbohydrate metabolism in streptozotocin-(STZ)-induced diabetic rats. Further, RRP extracts were prepared in water (RRPW), in 50% ethanol (RRP50), and in 100% ethanol (RRP100), respectively, and compared for their actions in diabetic rats. The oral treatment of RRP (5 mg/kg b.w./d) to diabetic rats for 21 days resulted in a significant decline in blood glucose by 67% compared to diabetic control rats (P < 0.05). The altered activities of glucokinase, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and acetyl CoA carboxylase (ACC) in the livers of diabetic rats were reversed significantly to near-normal levels by the administration of RRP (P < 0.05). Among the three RRP extracts, RRP100 was the most effective in terms of hypoglycemic action. However, the administration of RRP to diabetic rats did not improve insulin production. The modulatory effects of RRP100 on the attenuation of carbohydrate enzyme activities appear to hold promise for widespread use for the treatment of diabetes in the future.
Acetyl-CoA Carboxylase
;
Animals
;
Blood Glucose
;
Carbohydrate Metabolism
;
Ethanol
;
Glucokinase
;
Gluconates
;
Glucosephosphate Dehydrogenase
;
Hypoglycemic Agents
;
Insulin
;
Liver
;
Medicine, East Asian Traditional
;
Phosphogluconate Dehydrogenase
;
Rats
;
Thirst
;
Water