Dataset Information

Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2).

ABSTRACT:

Objective

We investigated the natural history of glucokinase (GCK)-related maturity-onset diabetes of the young type 2 (MODY2), notably the factors associated with deterioration of hyperglycemia over time.

Research design and methods

We report an 11-year follow-up of glucose tolerance and indexes of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects.

Results

The variation between tests of glucose tolerance (expressed as the area under the glucose curve) was 6.9 +/- 3.2% (mean +/- SEM), but individual results ranged from -20 to 61%. Deterioration of glucose tolerance between tests was associated with decreased insulin sensitivity, while insulin secretion remained stable.

Conclusions

Glucose tolerance can remain stable over many years in subjects with MODY2 due to the relative stability of the GCK-related beta-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and in the long-term evolution of the disorder.

SUBMITTER: Martin D

PROVIDER: S-EPMC2453674 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2).

Martin Delphine D Bellanné-Chantelot Christine C Deschamps Inge I Froguel Philippe P Robert Jean-Jacques JJ Velho Gilberto G

Diabetes care 20080414 7

<h4>Objective</h4>We investigated the natural history of glucokinase (GCK)-related maturity-onset diabetes of the young type 2 (MODY2), notably the factors associated with deterioration of hyperglycemia over time.<h4>Research design and methods</h4>We report an 11-year follow-up of glucose tolerance and indexes of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects.<h4>Results</h4>The variation between tests of glucose tolerance (expressed as ...[more]

PMID: 18411240

Similar Datasets

Project description:Aims/introductionSrc, a non-receptor tyrosine kinase, regulates a wide range of cellular functions, and hyperactivity of Src is involved in impaired glucose metabolism in pancreatic ?-cells. However, the physiological role of Src in glucose metabolism in normal, unstressed ?-cells remains unclear. In the present study, we investigated the role of Src in insulin secretion and glucose metabolism.Materials and methodsSrc was downregulated using small interfering ribonucleic acid in INS-1 cells, and glucose-induced insulin secretion, adenosine triphosphate content, intracellular calcium concentration, glucose utilization and glucokinase activity were measured. Expression levels of messenger ribonucleic acid and protein of glucokinase were examined by semiquantitative real-time polymerase chain reaction and immunoblotting, respectively. Cells were fractionated by digitonin treatment, and subcellular localization of glucokinase was examined by immunoblotting. Interaction between glucokinase and neuronal nitric oxide synthase was estimated by immunoprecipitation.ResultsIn Src downregulated INS-1 cells, glucose-induced insulin secretion was impaired, whereas insulin secretion induced by high K(+) was not affected. Intracellular adenosine triphosphate content and elevation of intracellular calcium concentration by glucose stimulation were suppressed by Src downregulation. Src downregulation reduced glucose utilization in the presence of high glucose, which was accompanied by a reduction in glucokinase activity without affecting its expression. However, Src downregulation reduced glucokinase in soluble, cytoplasmic fraction, and increased it in pellet containing intaracellular organelles. In addition, interaction between glucokinase and neuronal nitric oxide synthase was facilitated by Src downregulation.ConclusionsSrc plays an important role in glucose-induced insulin secretion in pancreatic ?-cells through maintaining subcellular localization and activity of glucokinase.

Project description:Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is a herbal medicine that has many potential pharmacological effects. The effect of KP extract on blood glucose level in rodent was reported. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3',4'-pentamethoxyflavone (PMF) and 5,7,4'-trimethoxylflavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. Blood glucose levels of volunteers at 120 min after glucose loading were able to be returned to initial levels in placebo, KP 90 mg/day, and KP 180 mg/day groups both at baseline and 28-days of administration. The results of the pharmacokinetic study revealed that only TMF and PMF, but not 5,7-dimethoxyflavone (DMF) levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2-3 h. The maximum concentration (Cmax), area under the curve of blood concentration and time (AUC), and time to maximum concentration (Tmax) values of PMF and TMF estimated for the 180 mg/day dose were 71.2 ± 11.3, 63.0 ± 18.0 ng/mL; 291.9 ± 48.2, 412.2 ± 203.7 ng∙h/mL; and 4.02 ± 0.37, 6.03 ± 0.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on the glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.

Dataset Information

Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2).

Objective

Research design and methods

Results

Conclusions

Publications

Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets