Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.
The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.
Kong
Won-Ho
WH
Biomedical Engineering Interdisciplinary Course, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Oh
Seung-Hoon
SH
Ahn
You-Ran
YR
Kim
Kwang-Won
KW
Kim
Jin-Hoon
JH
Seo
Soo-Won
SW
D017485:1-Deoxynojirimycin / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D012831:Bombyx / Q000737:chemistry; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D017485:1-Deoxynojirimycin