NO-1886 decreases ectopic lipid deposition and protects pancreatic beta cells in diet-induced diabetic swine.

Abstract

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.

• Authors: W Yin, D Liao, M Kusunoki, S Xi, K Tsutsumi, Z Wang, X Lian, T Koike, J Fan, Y Yang, C Tang
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 180 Issue 3 Pg. 399-408 (Mar 2004) ISSN: 0022-0795 [Print] England
• PMID: 15012594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Dietary Carbohydrates
• Dietary Fats
• Hypoglycemic Agents
• Organophosphorus Compounds
• 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide

Topics

• Animals
• Benzamides (pharmacology)
• Diabetes Mellitus (pathology)
• Dietary Carbohydrates (administration & dosage)
• Dietary Fats (administration & dosage)
• Hypoglycemic Agents (pharmacology)
• Insulin Resistance
• Islets of Langerhans (drug effects, metabolism, pathology)
• Lipid Metabolism
• Liver (metabolism)
• Male
• Models, Animal
• Muscle, Skeletal (metabolism)
• Myocardium (metabolism)
• Organophosphorus Compounds (pharmacology)
• Swine, Miniature