title: Physiological characterization of the human EndoC-βH1 β-cell line.
abstract: In the new human EndoC-βH1 β-cell line, a detailed analysis of the physiological characteristics was performed. This new human β-cell line expressed all target structures on the gene and protein level, which are crucial for physiological function and insulin secretion induced by glucose and other secretagogues. Glucose influx measurements revealed an excellent uptake capacity of EndoC-βH1 β-cells by the Glut1 and Glut2 glucose transporters. A high expression level of glucokinase enabled efficient glucose phosphorylation, increasing the ATP/ADP ratio along with stimulation of insulin secretion in the physiological glucose concentration range. The EC50 value of glucose for insulin secretion was 10.3 mM. Mannoheptulose, a specific glucokinase inhibitor, blocked glucose-induced insulin secretion (GSIS). The nutrient insulin secretagogues l-leucine and 2-ketoisocaproate also stimulated insulin secretion, with a potentiating effect of l-glutamine. The Kir 6.2 potassium channel blocker glibenclamide and Bay K 8644, an opener of the voltage-sensitive Ca(2+) channel significantly potentiated GSIS. Potentiation of GSIS by IBMX and forskolin went along with a strong stimulation of cAMP generation. In conclusion, the new human EndoC-βH1 β-cell line fully mirrors the analogous physiological characteristics of primary mouse, rat and human β-cells. Thus, this new human EndoC-βH1 β-cell line is very well suited for physiological β-cell studies.
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gurgul-Convey
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Kaminski
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: lenzen.sigurd@mh-hannover.de.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lenzen
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D001692:Biological Transport; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D018703:Founder Effect; D015870:Gene Expression; D005941:Glucokinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D007651:Keto Acids / Q000378:metabolism / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology; D008356:Mannoheptulose / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D015056:1-Methyl-3-isobutylxanthine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015220:Calcium Channels; D005576:Colforsin; D005941:Glucokinase; D005947:Glucose; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D005973:Glutamine; D005905:Glyburide; D007328:Insulin; D007651:Keto Acids; D007930:Leucine; D008356:Mannoheptulose; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C495677:SLC2A1 protein, human; C495680:SLC2A2 protein, human; C013082:alpha-ketoisocaproic acid
keywords: Diabetes; Glucose responsiveness; Human EndoC-βH1 β-cells; Insulin secretion