title: Obesity as an Early Symptom of the AMIS Syndrome.
abstract: 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. Postprandial hyperglycemia ensues, with compensatory hyperinsulinemia, resultant hyperlipidemia and elevated free radical stress. Storage of nutrient energy shifts from glycogen in muscle to fat. Chronic AMIS results in adiposity, occurs with age, is accelerated with sucrose supplement, and prevented by a synergistic antioxidant. Exercise reverses AMIS, as do pharmaceuticals that mimic the "feeding signals". The AMIS syndrome develops as a sequence of pathologies based on the consequences of absence of HISS action, including adiposity as the earliest symptom. Cardiac dysfunction, hypertension, hypercholesterolemia, and fatty liver are related to lack of HISS action. The AMIS syndrome hypothesis is mechanistic-based and accounts for the major pathologies associated with prediabetes, obesity, diabetes and metabolic syndrome. AMIS can be diagnosed, prevented and treated.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. wlautt@cc.umanitoba.ca.
authors.forename: W Wayne
authors.initials: WW
authors.lastname: Lautt
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, A224-753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada. h.helen.wang@med.umanitoba.ca.
authors.forename: Hui Helen
authors.initials: HH
authors.lastname: Wang
keywords: AMIS syndrome (Absence of Meal-induced Insulin Sensitization); Hepatic Insulin Sensitizing Substance (HISS); Meal-induced Insulin Sensitization (MIS); diabetes; hepatic parasympathetic neuropathy; hyperinsulinemia; insulin resistance; metabolic syndrome; obesity; prediabetes; rapid insulin sensitivity test (RIST)