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Postprandial insulin resistance as an early predictor of cardiovascular risk.

Lautt WW - Ther Clin Risk Manag (2007)

Bottom Line: The normal response to a mixed meal includes a doubling of insulin action secondary to insulin-induced release of a putative hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle.HISS is released only in the fed state and accounts for meal-induced insulin sensitization.HISS-dependent insulin resistance represents a novel hypothesis and suggests a new diagnostic and therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba Winnipeg, Manitoba, Canada.

ABSTRACT
Insulin resistance, hyperglycemia, hyperinsulinemia, hyperlipidemia and oxidative stress are risk factors related to cardiovascular diseases including congestive heart failure, myocardial infarction, ventricular hypertrophy, endothelial nitric oxide impairment in systemic blood vessels and the heart, atherosclerosis, and hypercoagulability of blood. The traditional focus on insulin sensitivity and blood levels of markers of risk determined in the fasted state is inconsistent with the large volume of recent data that indicates that the metabolic defect in the pre-diabetic and diabetic condition relates more strongly to postprandial deficiency than to the fasting state. Risk factors for adverse cardiovascular events can be detected in the pre-diabetic insulin-resistant subject based upon the metabolic response to a test meal even in the absence of altered fasting parameters. The normal response to a mixed meal includes a doubling of insulin action secondary to insulin-induced release of a putative hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle. HISS is released only in the fed state and accounts for meal-induced insulin sensitization. Blockade of HISS release leads to a condition referred to as HISS-dependent insulin resistance, which is suggested as the primary postprandial metabolic defect, accounting for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress in the pre-diabetic and diabetic condition. HISS-dependent insulin resistance represents a novel hypothesis and suggests a new diagnostic and therapeutic target.

No MeSH data available.


Related in: MedlinePlus

Feeding results in an increase of hepatic glutathione (GSH) and a parasympathetic signal to the liver that acts, via acetylcholine, on muscarinic receptors to activate NO release which, in turn, activates adenylyl cyclase. Both of these signals are permissive and both are needed in order that insulin can cause the release of hepatic insulin sensitizing substance (HISS). HISS acts selectively on skeletal muscle. Blockade of any portion of these pathways leads to blockade of HISS release and a state of HISS-dependent insulin resistance which is physiologically regulated to occur in the fasted state but, when not activated by feeding, is suggested to account for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress.
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fig1: Feeding results in an increase of hepatic glutathione (GSH) and a parasympathetic signal to the liver that acts, via acetylcholine, on muscarinic receptors to activate NO release which, in turn, activates adenylyl cyclase. Both of these signals are permissive and both are needed in order that insulin can cause the release of hepatic insulin sensitizing substance (HISS). HISS acts selectively on skeletal muscle. Blockade of any portion of these pathways leads to blockade of HISS release and a state of HISS-dependent insulin resistance which is physiologically regulated to occur in the fasted state but, when not activated by feeding, is suggested to account for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress.

Mentions: The permissive feeding signal (Figure 1), delivered to the liver through the parasympathetic nerves acts via muscarinic receptor activation and generation of hepatic nitric oxide which then results in the insulin dose-related release of HISS (Sadri and Lautt 1999; Guarino et al 2003). The nitric oxide acts through hepatic guanylyl cyclase (Correia et al 2002; Guarino et al 2004). Hepatic glutathione level, which decreases significantly with fasting and rapidly increases following re-feeding is also an essential component of the feeding response in rats (Guarino et al 2003; Lautt et al 2005; Sadri et al 2006). The mechanism of regulation of hepatic glutathione in response to feeding is unknown.


Postprandial insulin resistance as an early predictor of cardiovascular risk.

Lautt WW - Ther Clin Risk Manag (2007)

Feeding results in an increase of hepatic glutathione (GSH) and a parasympathetic signal to the liver that acts, via acetylcholine, on muscarinic receptors to activate NO release which, in turn, activates adenylyl cyclase. Both of these signals are permissive and both are needed in order that insulin can cause the release of hepatic insulin sensitizing substance (HISS). HISS acts selectively on skeletal muscle. Blockade of any portion of these pathways leads to blockade of HISS release and a state of HISS-dependent insulin resistance which is physiologically regulated to occur in the fasted state but, when not activated by feeding, is suggested to account for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376071&req=5

fig1: Feeding results in an increase of hepatic glutathione (GSH) and a parasympathetic signal to the liver that acts, via acetylcholine, on muscarinic receptors to activate NO release which, in turn, activates adenylyl cyclase. Both of these signals are permissive and both are needed in order that insulin can cause the release of hepatic insulin sensitizing substance (HISS). HISS acts selectively on skeletal muscle. Blockade of any portion of these pathways leads to blockade of HISS release and a state of HISS-dependent insulin resistance which is physiologically regulated to occur in the fasted state but, when not activated by feeding, is suggested to account for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress.
Mentions: The permissive feeding signal (Figure 1), delivered to the liver through the parasympathetic nerves acts via muscarinic receptor activation and generation of hepatic nitric oxide which then results in the insulin dose-related release of HISS (Sadri and Lautt 1999; Guarino et al 2003). The nitric oxide acts through hepatic guanylyl cyclase (Correia et al 2002; Guarino et al 2004). Hepatic glutathione level, which decreases significantly with fasting and rapidly increases following re-feeding is also an essential component of the feeding response in rats (Guarino et al 2003; Lautt et al 2005; Sadri et al 2006). The mechanism of regulation of hepatic glutathione in response to feeding is unknown.

Bottom Line: The normal response to a mixed meal includes a doubling of insulin action secondary to insulin-induced release of a putative hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle.HISS is released only in the fed state and accounts for meal-induced insulin sensitization.HISS-dependent insulin resistance represents a novel hypothesis and suggests a new diagnostic and therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba Winnipeg, Manitoba, Canada.

ABSTRACT
Insulin resistance, hyperglycemia, hyperinsulinemia, hyperlipidemia and oxidative stress are risk factors related to cardiovascular diseases including congestive heart failure, myocardial infarction, ventricular hypertrophy, endothelial nitric oxide impairment in systemic blood vessels and the heart, atherosclerosis, and hypercoagulability of blood. The traditional focus on insulin sensitivity and blood levels of markers of risk determined in the fasted state is inconsistent with the large volume of recent data that indicates that the metabolic defect in the pre-diabetic and diabetic condition relates more strongly to postprandial deficiency than to the fasting state. Risk factors for adverse cardiovascular events can be detected in the pre-diabetic insulin-resistant subject based upon the metabolic response to a test meal even in the absence of altered fasting parameters. The normal response to a mixed meal includes a doubling of insulin action secondary to insulin-induced release of a putative hepatic insulin sensitizing substance (HISS) that acts selectively on skeletal muscle. HISS is released only in the fed state and accounts for meal-induced insulin sensitization. Blockade of HISS release leads to a condition referred to as HISS-dependent insulin resistance, which is suggested as the primary postprandial metabolic defect, accounting for postprandial hyperglycemia, hyperinsulinemia, hyperlipidemia, and increased oxidative stress in the pre-diabetic and diabetic condition. HISS-dependent insulin resistance represents a novel hypothesis and suggests a new diagnostic and therapeutic target.

No MeSH data available.


Related in: MedlinePlus