@article{05bfa020335711df8ed1000ea68e967b,
title = "Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor",
abstract = "AIMS/HYPOTHESIS: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. METHODS: We compared GLP-1 and GIP concentrations measured at five time-points during a 75 g OGTT in 49 participants having GCK mutations with those of 28 familial controls. Mathematical modelling of glucose, insulin and C-peptide was used to estimate basal insulin secretion rate (BSR), total insulin secretion (TIS), beta cell glucose sensitivity, potentiation factor and insulin secretion rate (ISR). RESULTS: GIP and GLP-1 profiles during the OGTT were similar in GCK mutation carriers and controls (p = 0.52 and p = 0.44, respectively). Modelled variables of beta cell function showed a reduction in beta cell glucose sensitivity (87 pmol min(-1) m(-2) [mmol/l](-1) [95% CI 66-108] vs 183 pmol min(-1) m(-2) [mmol/l](-1) [95% CI 155-211], p < 0.001) and potentiation factor (1.5 min [95% CI 1.2-1.8] vs 2.2 min [95% CI 1.8-2.7], p = 0.007) but no change in BSR or TIS. The glucose/ISR curve was right-shifted in GCK mutation carriers. CONCLUSIONS/INTERPRETATION: Glucokinase, the major pancreatic glucose sensor, is not the main gut glucose sensor. By modelling OGTT data in GCK mutation carriers we were able to distinguish a specific beta cell glucose-sensing defect. Our data suggest a reduction in potentiation of insulin secretion by glucose that is independent of differences in incretin hormone release.",
author = "R Murphy and A Tura and Clark, {P M} and Holst, {Jens Juul} and A Mari and Hattersley, {A T}",
note = "Keywords: Adolescent; Adult; Aged; Biosensing Techniques; C-Peptide; Female; Glucokinase; Glucose; Humans; Incretins; Insulin; Insulin-Secreting Cells; Intestines; Male; Middle Aged; Mutation; Pancreas; Young Adult",
year = "2008",
doi = "10.1007/s00125-008-1183-9",
language = "English",
volume = "52",
pages = "154--9",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "1",
}