Dataset Information

Ingestion of a moderate high-sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon-like peptide-1 secretion.

ABSTRACT:

Unlabelled

Aims/Introduction:? Excessive intake of sucrose can cause severe health issues, such as diabetes mellitus. In animal studies, consumption of a high-sucrose diet (SUC) has been shown to cause obesity, insulin resistance and glucose intolerance. However, several in vivo experiments have been carried out using diets with much higher sucrose contents (50-70% of the total calories) than are typically ingested by humans. In the present study, we examined the effects of a moderate SUC on glucose metabolism and the underlying mechanism.

Materials and methods

? C57BL/6J mice received a SUC (38.5% sucrose), a high-starch diet (ST) or a control diet for 5?weeks. We assessed glucose tolerance, incretin secretion and liver glucose metabolism.

Results

? An oral glucose tolerance test (OGTT) showed that plasma glucose levels in the early phase were significantly higher in SUC-fed mice than in ST-fed or control mice, with no change in plasma insulin levels at any stage. SUC-fed mice showed a significant improvement in insulin sensitivity. Glucagon-like peptide-1 (GLP-1) secretion 15?min after oral glucose administration was significantly lower in SUC-fed mice than in ST-fed or control mice. Hepatic glucokinase (GCK) activity was significantly reduced in SUC-fed mice. During the OGTT, the accumulation of glycogen in the liver was suppressed in SUC-fed mice in a time-dependent manner.

Conclusions

? These results indicate that mice that consume a moderate SUC show glucose intolerance with a reduction in hepatic GCK activity and impairment in GLP-1 secretion. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00208.x, 2012).

SUBMITTER: Sakamoto E

PROVIDER: S-EPMC4019243 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ingestion of a moderate high-sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon-like peptide-1 secretion.

Sakamoto Eriko E Seino Yusuke Y Fukami Ayako A Mizutani Naohiro N Tsunekawa Shin S Ishikawa Kota K Ogata Hidetada H Uenishi Eita E Kamiya Hideki H Hamada Yoji Y Sato Hiroyuki H Harada Norio N Toyoda Yukiyasu Y Miwa Ichitomo I Nakamura Jiro J Inagaki Nobuya N Oiso Yutaka Y Ozaki Nobuaki N

Journal of diabetes investigation 20121001 5

<h4>Unlabelled</h4>Aims/Introduction: Excessive intake of sucrose can cause severe health issues, such as diabetes mellitus. In animal studies, consumption of a high-sucrose diet (SUC) has been shown to cause obesity, insulin resistance and glucose intolerance. However, several in vivo experiments have been carried out using diets with much higher sucrose contents (50-70% of the total calories) than are typically ingested by humans. In the present study, we examined the effects of a moderate SU ...[more]

PMID: 24843603

Similar Datasets

Project description:ObjectiveWhile the molecular events controlling insulin secretion from β-cells have been documented in detail, the exact mechanisms governing glucagon release by α-cells are understood only partially. This is a critical knowledge gap, as the normal suppression of glucagon secretion by elevated glucose levels fails in type 2 diabetes (T2D) patients, contributing to hyperglycemia through stimulation of hepatic glucose production. A critical role of glycolytic flux in regulating glucagon secretion was supported by recent studies in which manipulation of the activity and expression of the glycolytic enzyme glucokinase altered the setpoint for glucose-suppression of glucagon secretion (GSGS). Given this precedent, we hypothesized that genetic activation of glucokinase specifically in α-cells would enhance GSGS and mitigate T2D hyperglucagonemia.MethodsWe derived an inducible, α-cell-specific glucokinase activating mutant mouse model (GckLoxPGck∗/LoxPGck∗; Gcg-CreERT2; henceforth referred to as "α-mutGCK") in which the wild-type glucokinase gene (GCK) is conditionally replaced with a glucokinase mutant allele containing the ins454A activating mutation (Gck∗), a mutation that increases the affinity of glucokinase for glucose by almost 7-fold. The effects of α-cell GCK activation on glucose homeostasis, hormone secretion, islet morphology, and islet numbers were assessed using both in vivo and ex vivo assays. Additionally, the effect of α-cell GCK activation on GSGS was investigated under diabetogenic conditions of high-fat diet (HFD) feeding that dysregulate glucagon secretion.ResultsOur study shows that α-mutGCK mice have enhanced GSGS in vivo and ex vivo, independent of alterations in insulin levels and secretion, islet hormone content, islet morphology, or islet number. α-mutGCK mice maintained on HFD displayed improvements in glucagonemia compared to controls, which developed the expected obesity, glucose intolerance, elevated fasting blood glucose, hyperinsulinemia, and hyperglucagonemia.ConclusionsUsing our novel α-cell specific activation of GCK mouse model, we have provided additional support to demonstrate that the glycolytic enzyme glucokinase is a key determinant in glucose sensing within α-cells to regulate glucagon secretion. Our results contribute to our fundamental understanding of α-cell biology by providing greater insight into the regulation of glucagon secretion through α-cell intrinsic mechanisms via glucokinase. Furthermore, our HFD results underscore the potential of glucokinase as a druggable target which, given the ongoing development of allosteric glucokinase activators (GKAs) for T2D treatment, could help mitigate hyperglucagonemia and potentially improve blood glucose homeostasis.

Dataset Information

Ingestion of a moderate high-sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon-like peptide-1 secretion.

Unlabelled

Materials and methods

Results

Conclusions

Publications

Ingestion of a moderate high-sucrose diet results in glucose intolerance with reduced liver glucokinase activity and impaired glucagon-like peptide-1 secretion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets