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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

The RIST index (mg glucose/kg body weight required to maintain euglycemia after a bolus of 50 mU/kg of insulin) increased 90 minutes after administration of a mixed liquid test meal via an indwelling gastric catheter in conscious unrestrained rats. Atropine (1 mg/kg), which blocks release of hepatic insulin sensitizing substance (HISS), completely eliminated the meal-induced insulin sensitization (MIS). The same report showed that sucrose or glucose were ineffective in activating MIS. Prior surgical denervation of the liver blocked MIS from developing (Sadri et al 2006).
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fig2: The RIST index (mg glucose/kg body weight required to maintain euglycemia after a bolus of 50 mU/kg of insulin) increased 90 minutes after administration of a mixed liquid test meal via an indwelling gastric catheter in conscious unrestrained rats. Atropine (1 mg/kg), which blocks release of hepatic insulin sensitizing substance (HISS), completely eliminated the meal-induced insulin sensitization (MIS). The same report showed that sucrose or glucose were ineffective in activating MIS. Prior surgical denervation of the liver blocked MIS from developing (Sadri et al 2006).

Mentions: In a recent study we utilized a liquid test meal administered through a gastric catheter to quantitate MIS in both conscious and anesthetized rats by determining insulin sensitivity before and after the meal (Sadri et al 2006). A mixed liquid test meal, but not sucrose or glucose, resulted in MIS that could be completely reversed by atropine administration (Figure 2). The insulin sensitivity index increased in response to feeding and was reversed completely back to fasting levels of sensitivity by atropine. Similarly, prior denervation of the liver completely prevented the MIS process from occurring, thereby confirming the central role of hepatic parasympathetic nerves in the feeding signal. MIS has also recently been shown to occur in healthy male volunteers and blockade of MIS has been confirmed to occur in humans subsequent to atropine administration (Patarrao et al 2005).


Postprandial insulin resistance as an early predictor of cardiovascular risk.

Lautt WW - Ther Clin Risk Manag (2007)

The RIST index (mg glucose/kg body weight required to maintain euglycemia after a bolus of 50 mU/kg of insulin) increased 90 minutes after administration of a mixed liquid test meal via an indwelling gastric catheter in conscious unrestrained rats. Atropine (1 mg/kg), which blocks release of hepatic insulin sensitizing substance (HISS), completely eliminated the meal-induced insulin sensitization (MIS). The same report showed that sucrose or glucose were ineffective in activating MIS. Prior surgical denervation of the liver blocked MIS from developing (Sadri et al 2006).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: The RIST index (mg glucose/kg body weight required to maintain euglycemia after a bolus of 50 mU/kg of insulin) increased 90 minutes after administration of a mixed liquid test meal via an indwelling gastric catheter in conscious unrestrained rats. Atropine (1 mg/kg), which blocks release of hepatic insulin sensitizing substance (HISS), completely eliminated the meal-induced insulin sensitization (MIS). The same report showed that sucrose or glucose were ineffective in activating MIS. Prior surgical denervation of the liver blocked MIS from developing (Sadri et al 2006).
Mentions: In a recent study we utilized a liquid test meal administered through a gastric catheter to quantitate MIS in both conscious and anesthetized rats by determining insulin sensitivity before and after the meal (Sadri et al 2006). A mixed liquid test meal, but not sucrose or glucose, resulted in MIS that could be completely reversed by atropine administration (Figure 2). The insulin sensitivity index increased in response to feeding and was reversed completely back to fasting levels of sensitivity by atropine. Similarly, prior denervation of the liver completely prevented the MIS process from occurring, thereby confirming the central role of hepatic parasympathetic nerves in the feeding signal. MIS has also recently been shown to occur in healthy male volunteers and blockade of MIS has been confirmed to occur in humans subsequent to atropine administration (Patarrao et al 2005).

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