Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice.
1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol-treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/- 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Takahashi
H
H
Department of Clinical Sciences, Kansai Medical University, Osaka, Japan.
Nakano
K
K
Yasuda
T
T
Komiyama
Y
Y
Murakami
T
T
Nishimura
M
M
Nakanishi
T
T
Sakamoto
M
M
Nanbu
A
A
Yoshimura
M
M
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D050260:Carbohydrate Metabolism; D002302:Cardiac Output / Q000187:drug effects; D002354:Carteolol / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D004435:Eating / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002354:Carteolol; D005947:Glucose