Recent evidence has indicated that total fiber intake is inversely related to
type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed
guar gum (PHGG), a water-soluble
dietary fiber, on the occurrence of diabetes and its complications,
fatty liver and nephropathy. We also identified predictive serum
biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human
non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks.
Body weight, food intake, oral
glucose tolerance test, plasma
insulin levels, and urine
glucose and
protein levels were regularly measured. Oral
glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the experiment and every 4 weeks after overnight fasting during the experiments. PHGG treatment affected neither meal patterns nor the
body weight of OLETF and LETO rats. Repeated measure analysis of variance revealed significant differences in fasting plasma
glucose and plasma
glucose at 2 h after OGTT between control OLETF (OLETF-C) rats and OLETF rats treated with PHGG (OLETF-F). The
glucose response determined by the area under the curve of OGTT was significantly greater in OLETF-C rats than that in OLETF-F rats at 25 weeks of age. HOMA-IR, an index of
insulin resistance, increased at 25 weeks of age in OLETF-C rats, while this increase was significantly inhibited in OLETF-F rats. At 62 weeks of age, PHGG treatment significantly improved hepatic steatosis as well as renal mesangial matrix accumulation in OLETF rats. To identify the risk marker for
diabetes mellitus by SELDI-TOF MS, we collected sera from 21-week-old individuals. Among the 12 specific peaks that were risk marker candidates for
diabetes mellitus, the m/z 13,720 peak was identified as that of cysteinylated
transthyretin by sequencing of four tryptic
peptides using tandem mass spectrometry and peak distribution around the m/z 13,720 peak in the SELDI-TOF spectra. In conclusion, we found that chronic treatment with PHGG improved
insulin resistance, delayed the onset of diabetes, and inhibited the development of
diabetic complications, as well as identified cysteinylated
transthyretin as a predictive
biomarker of treatment response to PHGG in OLETF rats.