Oddmund Søvik - Academia.edu (original) (raw)
Papers by Oddmund Søvik
Diabetes, 2008
OBJECTIVE—Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that m... more OBJECTIVE—Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes. RESEARCH DESIGN AND METHODS—We screened INS in 62 probands with MODY, 30 probands with suspected MODY, and 223 subjects from the Norwegian Childhood Diabetes Registry selected on the basis of autoantibody negativity or family history of diabetes. RESULTS—Among the MODY patients, we identified the INS mutation c.137G>A (R46Q) in a proband, his diabetic father, and a paternal aunt. They were diagnosed with diabetes at 20, 18, and 17 years of age, respectively, and are treated with small doses of insulin or diet only. In type 1 diabetic patients, we found the INS mutation c.163C>T (R55C) in a girl who at 10 years of age presented with ketoacidosis and insulin-dependent, GAD, and insulinoma-associated antigen-2 (IA-2) antibody-negative diabetes. Her mother had a de no...
Tidsskrift for Den Norske Laegeforening, 2005
Til tross for moderne behandling forekommer det fortsa dødsfall hos barn på grunn av diabetesketo... more Til tross for moderne behandling forekommer det fortsa dødsfall hos barn på grunn av diabetesketoacidose. I de senere år har identifikasjon og forebygging av risikofaktorer for utvikling av hjerneødem vaert sterkt betont. Man har spesielt vaert oppta av betydningen av natriumnivå og raske forandringer i serumosmolaritet når det gjelder risiko for å utvikle hjerneødem under behandling av diabetesketoacidose.
Blood, 2006
Noonan syndrome is characterized by short stature, facial dysmorphism, and cardiac defects. We an... more Noonan syndrome is characterized by short stature, facial dysmorphism, and cardiac defects. We and our colleagues discovered novel de novo germline KRAS mutations that introduce V14I, T58I, or D153V amino acid substitutions in individuals with NS and a P34R alteration in an individual with cardio-facio-cutaneous (CFC) syndrome, which has overlapping phenotypic features with NS. Recombinant V14I and T58I K-Ras proteins display defective intrinsic GTP hydrolysis and impaired responsiveness to the GTPase activating proteins (GAPs) p120 GAP and neurofibromin. We also found that V14I and T58I K-Ras render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage specific manner (Nature Genetics38, 331, 2006). We recently began interrogating the P34R and D153V K-Ras mutant proteins and a novel CFC-associated F156L K-Ras mutant protein. Both P34R and D153V K-Ras display normal levels of intrinsic GTP hydrolysis. In contrast, F15...
Tidsskrift for Den Norske Laegeforening, 2001
Background. Generalised oedema after introducing insulin therapy is an infrequent complication, u... more Background. Generalised oedema after introducing insulin therapy is an infrequent complication, usually appearing when large doses are used in underweight patients. The pathophysiology is unclear. Materials and methods. Two patients from two different hospitals are presented by case histories. A limited literature search was performed. Results. Patient 1. A 13-year-old girl was admitted with polyuria and polydipsia and a weight loss of 15 kg over six months. She had ankle oedema, dry scaling skin, weight 31.6 kg (2 kg below 2.5th centile), marked hyperglycaemia (60 mmol/ l), and ketonuria without acidosis. After one day with insulin infusion she was treated with subcutaneous injections, reaching after a few days a dose of 2 U/kg/day. She gradually developed generalised oedema and gained 20 kg over two weeks. From day 8 after admission she was treated with furosemide and from day 16 also with ephedrine. S-albumin reached a nadir of 25 g/l. The oedema gradually disappeared. The patien...
Tidsskrift for Den norske legeforening, 2020
Tidsskrift for Den norske legeforening, 2011
*Other members of the Norwegian Childhood Diabetes Study Group are listed in the appendix at the ... more *Other members of the Norwegian Childhood Diabetes Study Group are listed in the appendix at the end of the paper.
Binding of ATP at the active site of human pancreatic glucokinase – nucleotide-induced conformati... more Binding of ATP at the active site of human pancreatic glucokinase – nucleotide-induced conformational changes
Tidsskrift for Den Norske Laegeforening, 2005
Tidsskrift for Den Norske Laegeforening, 2001
Persisterende neonatal hyperinsulinemisk hypoglykemi kjennetegnes ved hyperfunksjon av insulinpro... more Persisterende neonatal hyperinsulinemisk hypoglykemi kjennetegnes ved hyperfunksjon av insulinprodusende β-celler, lokalisert enten fokalt eller diffust i pancreas. Med en anslå hyppighet på 1 : 50 000 levendefødte vil vi i Norge i gjennomsni se e tilfelle årlig. Utredning og behandling er komplisert, og med så få pasienter er det vanskelig for et nasjonalt senter å tilby den nødvendige ekspertise. Vi rapporterer tre tilfeller med persisterende neonatal hyperinsulinemisk hypoglykemi som ble henvist til behandling ved Höpital des Enfants Malades i Paris. To av barna ble funnet å ha fokal hyperinsulinisme. Disse ble behandlet med partiell reseksjon av pancreas, Undersøkelse og behandling av barn med kongeni hyperinsulinisme-til Paris for enhver pris? | Tidsskrift for Den norske legeforening
Journal of Biological Chemistry, 2013
Background: Glucokinase is a key player in carbohydrate metabolism, but how this enzyme is regula... more Background: Glucokinase is a key player in carbohydrate metabolism, but how this enzyme is regulated by post-translational modifications is largely unknown. Results: Glucokinase is SUMO-modified in vitro and in pancreatic -cells, increasing its activity and stability. Conclusion: SUMOylation of glucokinase is a novel form of modification, regulating its cellular stability and activity. Significance: SUMO conjugation of glucokinase may have an important regulatory function in pancreatic -cells. Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic -cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissuespecific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how posttranslational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 -cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of posttranslational modification of the enzyme, and it may have an important regulatory function in pancreatic -cells. Blood glucose levels are normally maintained within a very tight range (4-8 mM) by regulated homeostatic mechanisms
Acta Paediatrica, 1978
The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly se... more The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly selected infants admitted to a neonatal intensive care unit. The data were compared with those of normal newborn infants. Urinary cyclic AMP concentrations were significantly correlated with gestational age (all patients), and with birth weight (all patients except infants of diabetic mothers (IDMs)). The urinary cyclic AMP/creatine ratio increased from day 1 to day 3 in normal newborns and in IDMs, and tended to increase also in small-for-gestational age (SGA), low birth weight (LBW), and sick, term infants, although the changes in the latter groups were not statistically significant. Four infants studied with parallel determinations showed increased cyclic AMP/creatinine ratio from day 1 to day 3 both in plasma and urine. All urinary cyclic AMP/creatine ratios were lower than the corresponding ratios found in plasma. In LBW infants, there was an inverse relationship between urinary cyclic AMP and serum calcium. In IDMs a positive correlation was observed between urinary cyclic AMP and blood glucose concentration. In conclusion, the excretion of cyclic AMP in sick newborn infants is influenced by the following factors: gestational age, postnatal age, birth weight, and derangements of serum calcium and blood glucose concentrations.
Tidsskrift for Den norske legeforening, 2009
Diabetes, 2008
OBJECTIVE—Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that m... more OBJECTIVE—Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations in INS could also cause maturity-onset diabetes of the young (MODY) and autoantibody-negative type 1 diabetes. RESEARCH DESIGN AND METHODS—We screened INS in 62 probands with MODY, 30 probands with suspected MODY, and 223 subjects from the Norwegian Childhood Diabetes Registry selected on the basis of autoantibody negativity or family history of diabetes. RESULTS—Among the MODY patients, we identified the INS mutation c.137G>A (R46Q) in a proband, his diabetic father, and a paternal aunt. They were diagnosed with diabetes at 20, 18, and 17 years of age, respectively, and are treated with small doses of insulin or diet only. In type 1 diabetic patients, we found the INS mutation c.163C>T (R55C) in a girl who at 10 years of age presented with ketoacidosis and insulin-dependent, GAD, and insulinoma-associated antigen-2 (IA-2) antibody-negative diabetes. Her mother had a de no...
Tidsskrift for Den Norske Laegeforening, 2005
Til tross for moderne behandling forekommer det fortsa dødsfall hos barn på grunn av diabetesketo... more Til tross for moderne behandling forekommer det fortsa dødsfall hos barn på grunn av diabetesketoacidose. I de senere år har identifikasjon og forebygging av risikofaktorer for utvikling av hjerneødem vaert sterkt betont. Man har spesielt vaert oppta av betydningen av natriumnivå og raske forandringer i serumosmolaritet når det gjelder risiko for å utvikle hjerneødem under behandling av diabetesketoacidose.
Blood, 2006
Noonan syndrome is characterized by short stature, facial dysmorphism, and cardiac defects. We an... more Noonan syndrome is characterized by short stature, facial dysmorphism, and cardiac defects. We and our colleagues discovered novel de novo germline KRAS mutations that introduce V14I, T58I, or D153V amino acid substitutions in individuals with NS and a P34R alteration in an individual with cardio-facio-cutaneous (CFC) syndrome, which has overlapping phenotypic features with NS. Recombinant V14I and T58I K-Ras proteins display defective intrinsic GTP hydrolysis and impaired responsiveness to the GTPase activating proteins (GAPs) p120 GAP and neurofibromin. We also found that V14I and T58I K-Ras render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage specific manner (Nature Genetics38, 331, 2006). We recently began interrogating the P34R and D153V K-Ras mutant proteins and a novel CFC-associated F156L K-Ras mutant protein. Both P34R and D153V K-Ras display normal levels of intrinsic GTP hydrolysis. In contrast, F15...
Tidsskrift for Den Norske Laegeforening, 2001
Background. Generalised oedema after introducing insulin therapy is an infrequent complication, u... more Background. Generalised oedema after introducing insulin therapy is an infrequent complication, usually appearing when large doses are used in underweight patients. The pathophysiology is unclear. Materials and methods. Two patients from two different hospitals are presented by case histories. A limited literature search was performed. Results. Patient 1. A 13-year-old girl was admitted with polyuria and polydipsia and a weight loss of 15 kg over six months. She had ankle oedema, dry scaling skin, weight 31.6 kg (2 kg below 2.5th centile), marked hyperglycaemia (60 mmol/ l), and ketonuria without acidosis. After one day with insulin infusion she was treated with subcutaneous injections, reaching after a few days a dose of 2 U/kg/day. She gradually developed generalised oedema and gained 20 kg over two weeks. From day 8 after admission she was treated with furosemide and from day 16 also with ephedrine. S-albumin reached a nadir of 25 g/l. The oedema gradually disappeared. The patien...
Tidsskrift for Den norske legeforening, 2020
Tidsskrift for Den norske legeforening, 2011
*Other members of the Norwegian Childhood Diabetes Study Group are listed in the appendix at the ... more *Other members of the Norwegian Childhood Diabetes Study Group are listed in the appendix at the end of the paper.
Binding of ATP at the active site of human pancreatic glucokinase – nucleotide-induced conformati... more Binding of ATP at the active site of human pancreatic glucokinase – nucleotide-induced conformational changes
Tidsskrift for Den Norske Laegeforening, 2005
Tidsskrift for Den Norske Laegeforening, 2001
Persisterende neonatal hyperinsulinemisk hypoglykemi kjennetegnes ved hyperfunksjon av insulinpro... more Persisterende neonatal hyperinsulinemisk hypoglykemi kjennetegnes ved hyperfunksjon av insulinprodusende β-celler, lokalisert enten fokalt eller diffust i pancreas. Med en anslå hyppighet på 1 : 50 000 levendefødte vil vi i Norge i gjennomsni se e tilfelle årlig. Utredning og behandling er komplisert, og med så få pasienter er det vanskelig for et nasjonalt senter å tilby den nødvendige ekspertise. Vi rapporterer tre tilfeller med persisterende neonatal hyperinsulinemisk hypoglykemi som ble henvist til behandling ved Höpital des Enfants Malades i Paris. To av barna ble funnet å ha fokal hyperinsulinisme. Disse ble behandlet med partiell reseksjon av pancreas, Undersøkelse og behandling av barn med kongeni hyperinsulinisme-til Paris for enhver pris? | Tidsskrift for Den norske legeforening
Journal of Biological Chemistry, 2013
Background: Glucokinase is a key player in carbohydrate metabolism, but how this enzyme is regula... more Background: Glucokinase is a key player in carbohydrate metabolism, but how this enzyme is regulated by post-translational modifications is largely unknown. Results: Glucokinase is SUMO-modified in vitro and in pancreatic -cells, increasing its activity and stability. Conclusion: SUMOylation of glucokinase is a novel form of modification, regulating its cellular stability and activity. Significance: SUMO conjugation of glucokinase may have an important regulatory function in pancreatic -cells. Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic -cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissuespecific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how posttranslational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 -cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of posttranslational modification of the enzyme, and it may have an important regulatory function in pancreatic -cells. Blood glucose levels are normally maintained within a very tight range (4-8 mM) by regulated homeostatic mechanisms
Acta Paediatrica, 1978
The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly se... more The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly selected infants admitted to a neonatal intensive care unit. The data were compared with those of normal newborn infants. Urinary cyclic AMP concentrations were significantly correlated with gestational age (all patients), and with birth weight (all patients except infants of diabetic mothers (IDMs)). The urinary cyclic AMP/creatine ratio increased from day 1 to day 3 in normal newborns and in IDMs, and tended to increase also in small-for-gestational age (SGA), low birth weight (LBW), and sick, term infants, although the changes in the latter groups were not statistically significant. Four infants studied with parallel determinations showed increased cyclic AMP/creatinine ratio from day 1 to day 3 both in plasma and urine. All urinary cyclic AMP/creatine ratios were lower than the corresponding ratios found in plasma. In LBW infants, there was an inverse relationship between urinary cyclic AMP and serum calcium. In IDMs a positive correlation was observed between urinary cyclic AMP and blood glucose concentration. In conclusion, the excretion of cyclic AMP in sick newborn infants is influenced by the following factors: gestational age, postnatal age, birth weight, and derangements of serum calcium and blood glucose concentrations.
Tidsskrift for Den norske legeforening, 2009