BackgroundTrehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers.MethodsIn a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured.ResultsTrehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion.ConclusionsOur findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.
Summary Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/ HFD group were significantly lower than those in the DW/HFD group (p,0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.
SummaryWe previously performed animal studies that suggested that trehalose potentially prevents the development of metabolic syndrome in humans. To evaluate this possibility, we examined whether trehalose suppressed the progression of insulin resistance in a placebo-controlled, double-blind trial in 34 subjects with a body mass index (BMI) $23. The subjects were divided into two groups and were assigned to ingest either 10 g/d of trehalose or sucrose with meals for 12 wk. During the study, body composition and blood biochemical parameters were measured at week 0, 8, and 12. These parameters were also measured 4 wk after the end of intake to confirm the washout of test substances. In the trehalose group, blood glucose concentrations after a 2-h oral glucose tolerance test significantly decreased following 12 wk of intake in comparison with baseline values (0 wk). When a stratified analysis was performed in the subjects whose percentage of truncal fat approached the high end of the normal range, the change in body weight, waist circumference, and systolic blood pressure were significantly lower in the trehalose group than in the sucrose group. Our data indicated that a daily intake of 10 g of trehalose improved glucose tolerance and progress to insulin resistance. Furthermore, these results suggested that trehalose can potentially reduce the development of metabolic syndrome and associated lifestyle-related diseases, such as type 2 diabetes.
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