Obesity, syndrome X, and diabetes: the role of HISS-dependent insulin resistance altered by sucrose, an antioxidant cocktail, and age

• Published in: Canadian journal of physiology and pharmacology 2009-10, Vol.87 (10), p.873-882
• Main Authors: ZHI MING, LEGARE, Dallas J, WAYNE LAUTT, W
• Format: Article
• Language: English
• Subjects: Adipose Tissue - physiology; Aging - physiology; Animals; Antioxidants - pharmacology; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure - drug effects; Body Composition - drug effects; Body Weight - drug effects; Complications and side effects; Diabetes; Diabetes Mellitus - metabolism; Diet therapy; Eating - physiology; Fundamental and applied biological sciences. Psychology; Hyperinsulinism - metabolism; Insulin; Insulin - blood; Insulin Resistance - physiology; Lipid Metabolism - physiology; Male; Metabolic Syndrome - metabolism; Metabolic syndrome X; Obesity; Obesity - metabolism; Rats; Rats, Sprague-Dawley; Risk factors; Studies; Sucrose - administration & dosage; Sucrose - pharmacology; Triglycerides - blood; Type 2 diabetes; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/Y09-079

Absence of meal-induced insulin sensitization (AMIS) results in a predictable progression of dysfunctions, including postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X and diabetes. To test the 'AMIS syndrome' hypothesis we used 3 known means of producing graded and progressive changes in meal-induced insulin sensitization in rats. We used an aging model (9, 26, and 52 weeks), associated with a slow development of AMIS; a low-dose sucrose supplement model to accelerate the development of AMIS; and an antioxidant cocktail (S-adenosylmethionine, vitamin E, and vitamin C) to protect against the effect of the sucrose on meal-induced insulin sensitization. Adiposity was assessed from weighed regional fat masses and bioelectrical impedance. AMIS developed with age, was increased by sucrose supplementation, and was inhibited by the antioxidant cocktail. AMIS correlated with postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and with adiposity (r2 = 0.7-0.8) regardless of age or nutrient status. The range of degrees of AMIS, established over time with these models, afforded the tool with which to test the AMIS syndrome and further the argument that AMIS is the first metabolic defect that cumulatively leads to a predictable series of homeostatic disturbances and dysfunctions, including obesity and type 2 diabetes.