TY - JOUR
T1 - Effect of adipocyte β 3-adrenergic receptor activation on the type 2 diabetic MKR mice
AU - Kim, Hyunsook
AU - Pennisi, Patricia A.
AU - Gavrilova, Oksana
AU - Pack, Stephanie
AU - Jou, William
AU - Setser-Portas, Jennifer
AU - East-Palmer, Joyce
AU - Tang, Yan
AU - Manganiello, Vincent C.
AU - LeRoith, Derek
PY - 2006
Y1 - 2006
N2 - The antiobesity and antidiabetic effects of the β 3- adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β 3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β 3- adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β 3-adrenergic agonists in nonobese diabetic subjects.
AB - The antiobesity and antidiabetic effects of the β 3- adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a β 3-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that β 3- adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for β 3-adrenergic agonists in nonobese diabetic subjects.
KW - Insulin-like growth factor I receptor mutation
KW - Type 2 diabetes
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U2 - 10.1152/ajpendo.00344.2005
DO - 10.1152/ajpendo.00344.2005
M3 - Article
C2 - 16682489
AN - SCOPUS:33744933163
SN - 0193-1849
VL - 290
SP - E1227-E1236
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6
ER -
