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

Abstract

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)

Opposite effects of a glucokinase activator and metformin on glucose‐regulated gene expression in hepatocytes

“…Chronic feeding of animal models with fructose or sucrose has been found to either increase or decrease glucokinase protein or activity . In mice fed a high‐energy diet with fructose, we found lower liver glucokinase protein (Figure A).…”

Fructose induces glucose‐dependent insulinotropic polypeptide, glucagon‐like peptide‐1 and insulin secretion: Role of adenosine triphosphate‐sensitive K+ channels

“…Blood glucose levels were measured with ANTSENSE II (Bayer Medical, Leverkusen, Germany). Plasma total GIP and GLP‐1 levels were measured using the GIP (TOTAL) ELISA kit (Merck Millipore, Billerica, MA, USA) and an electrochemiluminescent sandwich immunoassay (Meso Scale Discovery, Gaithersburg, MD, USA) as previously described. Plasma insulin levels were determined by an ELISA kit (Morinaga, Tokyo, Japan).…”

A review of recent evidence relating to sugars, insulin resistance and diabetes

“…Both of these dietary treatments are so extreme; it is not surprising that metabolic abnormalities were observed. Another study fed mice with a diet providing 38.5% of energy as sucrose and observed elevated plasma glucose levels in the early phase of an oral glucose tolerance test (OGTT) indicative of insulin resistance or impaired insulin release [12]. However, the same study showed that sucrose feeding improved insulin sensitivity as assessed during an insulin tolerance test.…”