Acute and chronic treatment of L-isoleucine ameliorates glucose metabolism in glucose-intolerant and diabetic mice.
The administration of L-isoleucine (isoleucine) has been shown to induce hypoglycemia in normal rats. However, it remains to be elucidated whether isoleucine can improve the blood glucose level in glucose-intolerant or diabetic animals. In the present study, oral isoleucine significantly reduced the blood glucose level after an oral glucose challenge in normal mice, as well as in glucose-intolerant mice fed a high-fat diet (HFD) and db/db mice, a model of severe type 2 diabetes. Isoleucine treatment significantly augmented the blood insulin level after an oral glucose load in HFD mice, but not in normal or db/db mice, suggesting that its hypoglycemic activity was attributable to both insulinotropic and non-insulinotropic mechanisms. Chronic supplementation of isoleucine in mice on a high-fat/high-sucrose diet significantly reduced insulin release after an oral glucose challenge without any change in glucose tolerance curve, suggesting that isoleucine might have an insulin-sensitizing effect along with its acute hypoglycemic effect. These results indicate that both acute and chronic treatment with isoleucine is beneficial for glucose metabolism in glucose-intolerant and diabetic animals.
Ikehara
Osamu
O
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan.
Kawasaki
Noriko
N
Maezono
Katsumi
K
Komatsu
Mitsuhisa
M
Konishi
Atsushi
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007532:Isoleucine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013395:Sucrose / Q000008:administration & dosage
D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D007532:Isoleucine; D013395:Sucrose; D005947:Glucose