Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Oct;3(5):761-70.

Postprandial insulin resistance as an early predictor of cardiovascular risk

W Wayne Lautt  1
Affiliations

Postprandial insulin resistance as an early predictor of cardiovascular risk

W Wayne Lautt. Ther Clin Risk Manag. 2007 Oct.

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.

Keywords: HISS; hyperglycemia; hyperinsulinemia; hyperlipidemia; oxidative stress.

PubMed Disclaimer

Figures

Figure 1
Figure 1
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.
Figure 2
Figure 2
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).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. [ADA] ADA Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20:1183–97. - PubMed
    1. [ADA] ADA Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26:S5–20. - PubMed
    1. Anderson RA, Evans ML, Ellis GR, et al. The relationship between post-prandial lipeemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis. 2001;154:475–83. - PubMed
    1. Anderson EA, Hoffman RP, Balon TW, et al. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991;87:2246–52. - PMC - PubMed
    1. Anderson TJ, Meredith IT, Yeung AC, et al. The effect of cholesterol-lowering and antioxidant therapy on endothelial-dependent coronary vasomotion. N Engl J Med. 1995;332:488–93. - PubMed

LinkOut - more resources