Abstract
A series of in vivo and in vitro studies using animal and human models in the past 15 years have demonstrated that approximately 55% (~66% in humans) of the glucose disposal effect of an i.v. injection of insulin in the fed state is dependent on the action of a second hormone, hepatic insulin sensitizing substance (HISS), which is released from the liver and stimulates glucose uptake in muscle, heart and kidneys. Sensitization of the insulin response by a meal through release of HISS is called meal-induced insulin sensitization (MIS). Absence of HISS action results in postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, adiposity, increased free radical stress and a cluster of progressive metabolic and cardiovascular dysfunctions referred to as the AMIS (absence of meal-induced insulin sensitization) syndrome. Reduced HISS release accounts for the insulin resistance that occurs with aging and is made worse by physical inactivity and diets high in sucrose or fat. This brief review provides an update of major metabolic disturbances associated with aging due to reduction of HISS release, and the protection against these pathological changes in aging animals using a balanced synergistic antioxidant cocktail SAMEC (S-adenosylmethionine, vitamins E and C). The synergy amongst the components is consistent with the known benefits of antioxidants supplied by a mixed diet and acting through diverse mechanisms. Using only three constituents, SAMEC appears suitable as an antioxidant specifically targeting the AMIS syndrome.
Highlights
Aging and Age-Related Metabolic Dysfunctions: The Role of hepatic insulin sensitizing substance (HISS) and Absence of meal-induced insulin sensitization (AMIS)Aging is often, and unnecessarily, associated with predictable pathologies and reduced homeostatic capacity in multiple organs
We suggest that the initiating metabolic defect that leads progressively to the metabolic syndrome, diabetes, and multiple organ failure is a postprandial defect in glucose sequestration that results in nutrient energy being shifted from normal storage as glycogen in skeletal muscle to production and storage of lipids, and postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia and increased reactive oxidative stress ([7,9], see table 1 in ref [7])
Using an in vivo euglycemic clamp, the rapid insulin sensitivity test (RIST) [56], Lautt et al tested male Sprague Dawley rats at 9, 26, and 52 weeks of age to determine their dynamic response to insulin, which contains the HISS-dependent (HISS action) and HISS-independent components of insulin action
Summary
Unnecessarily, associated with predictable pathologies and reduced homeostatic capacity in multiple organs. Oxygenated radicals have a role in gene expression, cell oxidative injuries and cytotoxic activity of the immune system [5] Antioxidants, especially those in mixed diets, are associated with lowering oxidative stress, DNA damage, malignant transformation, and other parameters of cell damage in vitro, and lowering the incidence of certain types of cancer and degenerative diseases [6]. Understanding the physiology of HISS allows early diagnosis and intervention for many of the metabolic and cardiovascular dysfunctions associated with age. These studies show a very significant role for balanced antioxidant management to prevent some of the most debilitating health issues in the elderly
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