A synergistic, balanced antioxidant cocktail, protects aging rats from insulin resistance and absence of meal-induced insulin sensitization (AMIS) syndrome.

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.

Fatty Liver and Fatty Heart-Where do They Stand in the AMIS Syndrome?

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.

Obesity as an Early Symptom of the AMIS Syndrome.

We review evidence that the AMIS (Absence of Meal-induced Insulin Sensitization) syndrome describes a paradigm fundamental to development of obesity. The hypoglycemic response to a pulse of insulin is doubled after a meal as a result of Hepatic Insulin Sensitizing Substance (HISS), released from the liver to act selectively on muscle, heart and kidney. In the absence of HISS action, the hypoglycemic response to insulin is the same as in the fasted state, and only half of what it should be.

Current views concerning the influences of murine hepatic endothelial adhesive and cytotoxic properties on interactions between metastatic tumor cells and the liver.

Substantial recent experimental evidence has demonstrated the existence of reciprocal interactions between the microvascular bed of a specific organ and intravascular metastatic tumor cells through expression of adhesion molecules and nitric oxide release, resulting in a significant impact upon metastatic outcomes. This review summarizes the current findings of adhesive and cytotoxic endothelial-tumor cell interactions in the liver, the inducibility, zonal distribution and sinusoidal structural influences on the hepatic endothelial regulatory functions, and the effects of these functions on the formation of liver cancer metastases. New insights into the traditional cancer metastatic cascade are also discussed.

Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells.

Metastatic cancer cells seed the lung via blood vessels. Because endothelial cells generate nitric oxide (NO) in response to shear stress, we postulated that the arrest of cancer cells in the pulmonary microcirculation causes the release of NO in the lung. After intravenous injection of B16F1 melanoma cells, pulmonary NO increased sevenfold throughout 20 minutes and approached basal levels by 4 hours.