NO-1886 decreases ectopic lipid deposition and protects pancreatic beta cells in diet-induced diabetic swine.
The synthetic compound NO-1886 (ibrolipim) is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides. Recently, we found that NO-1886 also reduced plasma free fatty acids and glucose in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 treatment on ectopic lipid deposition and the islet pathology in miniature swine fed a high-fat/high-sucrose diet. Our results showed that feeding this diet to miniature swine caused insulin resistance, increased lipid deposition in non-adipose tissue, such as in the heart, skeletal muscle, liver and pancreas, and also caused pancreatic beta cell damage. However, supplementing 1% NO-1886 (200 mg/kg per day) into the high-fat/high-sucrose diet decreased ectopic lipid deposition, improved insulin resistance, and alleviated the beta cell damage. These results suggest that improvement of lipid disorder, non-adipose tissue steatosis and insulin resistance may be very important for the protection of beta cell damage. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistance syndrome.
Yin
W
W
Department of Biochemistry and Biotechnology, Nanhua University School of Life Sciences and Technology, Hengyang, Hunan 421001, China. wdy20012001@yahoo.com
Liao
D
D
Kusunoki
M
M
Xi
S
S
Tsutsumi
K
K
Wang
Z
Z
Lian
X
X
Koike
T
T
Fan
J
J
Yang
Y
Y
Tang
C
C
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000473:pathology*; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D013556:Swine, Miniature
D001549:Benzamides; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide