Meal-induced insulin sensitization (MIS) refers to the augmented glucose uptake response to insulin following a meal. Absence of MIS (AMIS) causes significant decrease in post-meal glucose disposal leading to postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, adiposity, increased free radical stress, and a cluster of progressive metabolic, vascular, and cardiac dysfunctions referred to as the AMIS syndrome. We tested the hypothesis that fat accumulation in the liver and heart is part of the AMIS syndrome. Questions examined in the study: (1) Is prediabetic fat accumulation in the heart and liver a component of the AMIS syndrome? (2) Is fatty liver a cause or consequence of peripheral insulin resistance? (3) Is early cardiac dysfunction in the AMIS syndrome attributable to fat accumulation in the heart? and (4) Can the synergistic antioxidant cocktail SAMEC (S-adenosylmethionine, vitamin E, and vitamin C), known to benefit MIS, affect cardiac and hepatic triglyceride levels? Four animal models of AMIS were used in aged male Sprague-Dawley rats (52 weeks ± sucrose ± SAMEC), compared with young controls (nine weeks). Fat accumulation in the heart was not significant and therefore cannot account for the early cardiac dysfunction. Hepatic triglycerides increased only in the most severe AMIS model but the small changes correlated with the much more rapidly developing peripheral adiposity. Systemic adiposity represents an early stage, whereas accumulation of cardiac and hepatic triglycerides represents a late stage of the prediabetic AMIS syndrome. Fat accumulation in the liver is a consequence, not a cause, of AMIS. SAMEC protected against the sucrose effects on whole body adiposity and hepatic lipid accumulation.
Keywords: S-adenosylmethionine; absence of meal-induced insulin sensitization (AMIS); hepatic insulin sensitizing substance (HISS); meal-induced insulin sensitization (MIS); non-alcoholic fatty liver disease (NAFLD); rapid insulin sensitivity test (RIST); vitamins E and C (SAMEC).