Whole body hyperthermia improves obesity-induced insulin resistance in diabetic mice.
OBJECTIVE
In this study, we examined the efficacy of whole body hyperthermia (WBH) on obesity-induced insulin resistance in diabetic mice.


METHODS
Male db/db mice were treated with WBH 3 times per week for 12 weeks. The rectal temperature of mice reached 38.0 degrees C 5 min after heating, and was kept at 38.0 degrees C for 30 min. At the end of each week, tail snip glucose levels were determined under fasting conditions. The GLUT-4 gene expression of muscle tissue was analyzed by real-time PCR.


RESULTS
(1) WBH-treated db/db mice showed a significant decrease in fasting blood glucose level as compared with untreated db/db mice (p < 0.01). (2) Plasma insulin levels in untreated db/db mice at the age of 10 weeks were significantly increased compared with those of db/+ mice (p < 0.0001). On the other hand, the reduction (31%) in insulin levels in WBH-treated mice indicated improved insulin sensitivity. (3) The ability of WBH to increase insulin sensitivity was further established in glucose tolerance tests and insulin tolerance tests. (4) Urine albumin of db/db mice significantly increased compared with those of db/+ mice at 18 weeks of age (p < 0.001). This increase in urinary albumin was significantly inhibited by WBH (p < 0.01). (5) WBH up-regulated the expression of GLUT4 mRNA in skeletal muscle.


CONCLUSIONS
Although the mechanisms have not yet been completely investigated, WBH may provide a new therapeutic or preventive modality against obesity-related diseases such as T2DM and metabolic or insulin resistance syndrome.
Kokura
Satoshi
S
Biomedical Safety Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. s-kokura@mpd.biglobe.ne.jp
Adachi
Satoko
S
Manabe
Emiko
E
Mizushima
Katsura
K
Hattori
Takeshi
T
Okuda
Toshimitsu
T
Nakabe
Nami
N
Handa
Osamu
O
Takagi
Tomohisa
T
Naito
Yuji
Y
Yoshida
Norimasa
N
Yoshikawa
Toshikazu
T
D000419:Albuminuria / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000628:therapy; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006979:Hyperthermia, Induced; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D014280:Triglycerides