Sensitization to insulin induced by β,β'-methyl-substituted hexadecanedioic acid (MEDICA 16) in obese Zucker rats in vivo

• Published in: Diabetes (New York, N.Y.) Vol. 46; no. 12; pp. 1958 - 1964
• Main Authors: MAYOREK, N, KALDERON, B, ITACH, E, BAR-TANA, J
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.1997
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Cholesterol - blood; Fatty acids; Fatty Acids, Nonesterified - blood; Glucose - biosynthesis; Glucose Clamp Technique; Hypolipidemic Agents - pharmacology; Insulin; Insulin - blood; Insulin - pharmacology; Insulin Resistance; Kinetics; Liver - drug effects; Liver - metabolism; Medical sciences; Metabolic diseases; Muscles - drug effects; Muscles - metabolism; Obesity; Obesity - metabolism; Palmitic Acid - blood; Palmitic Acids - pharmacology; Physiological aspects; Rats; Rats, Zucker; Triglycerides - blood; Animal model; Obesity; Pancreatic hormone; Adipose tissue; Rat; Glucose clamp technique; Long chain; Liver; Rodentia; Nutrition disorder; Lipids; Striated muscle; Fatty acids; Insulin; Target tissue resistance; Vertebrata; Mammalia; Complication; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.46.12.1958

Beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) consists of a nonmetabolizable long-chain fatty acid designed to probe the effect exerted by fatty acids on insulin sensitivity. The effect of MEDICA 16 was evaluated in insulin-resistant Zucker (fa/fa) rats in terms of liver, muscle, and adipose tissue response to clamped euglycemic hyperinsulinemia in vivo. Nontreated Zucker rats were insulin resistant, maintaining basal rates of total-body glucose disposal, glucose production in liver, free fatty acid (FFA) flux into plasma, and FFA reesterification in adipose tissue, irrespective of the insulin levels induced. MEDICA 16 treatment resulted in an insulin-induced decrease in hepatic glucose production, together with an insulin-induced increase in total-body glucose disposal. Intracellular reesterification of lipolysed FFA in adipose tissue was specifically activated by MEDICA 16, resulting in a pronounced decrease in FFA release, with a concomitant decrease in plasma FFA. In conclusion, MEDICA 16 treatment results in the sensitization of liver, muscle, and adipose tissue to insulin in an animal model for obesity-induced insulin resistance.