Metabolic consequences of hyperglycemia and insulin resistance

doi:10.1016/S1098-3597(07)80019-6

Clinical Cornerstone

Volume 8, Supplement 7, 2007, Pages S30-S42

https://doi.org/10.1016/S1098-3597(07)80019-6 Get rights and content

Insulin is a pleiotropic hormone that exerts a multitude of effects on metabolism and various cellular processes in the body. The main metabolic actions of insulin are to stimulate glucose uptake in skeletal muscle and the heart and to suppress the production of glucose and very-low-density lipoprotein in the liver. Other metabolic effects of insulin include inhibition of glucose release from the liver, inhibition of the release of free fatty acids (FFAs) from adipose tissue, and stimulation of the process by which amino acids are incorporated into protein. Insulin resistance (IR) is a condition in which defects in the action of insulin are such that normal levels of insulin do not trigger the signal for glucose absorption. An excess of FFAs is implicated in the pathogenesis of IR. The effects of this condition can have profound pathophysiologic effects on various organs and tissues of the body. For example, IR is associated with impaired insulin signaling, impaired fibrinolysis, and inflammation. The clinical consequences include hyperglycemia-induced tissue damage, hypertension, dyslipidemia, metabolic syndrome, and cardiovascular disease. Pharmacotherapies that target IR include metformin and the thiazolidinediones. Endocannabinoid antagonists, agents that target obesity and associated cardiovascular and metabolic risk factors, are currently being developed.

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Metabolic consequences of hyperglycemia and insulin resistance

Lancet

Clin Cornerstone

The metabolic syndrome. Lancet

Vascular dysfunction in diabetes mellitus. Lancet

Trends Immunol

Clinical effects of hyperglycemia in the cardiac surgery population: The Portland Diabetic Project. Endocr Pract

Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol

Am Heart J

Lipid and lipoprorein dysregulation in insulin resistant states. Clin Chim Acta

Metabolism

Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates. J Biol Chem

Endocrinol Metab Clin North Am

The cardiometabolic syndrome as a cardiovascular risk factor. Am J Med Sci

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Trends Neurosci

Life Sci

Lancet

Lancet

et al

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The pathobiology of diabetic complications: A unifying mechanism

Diabetes

Hypoglycemia

Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells

Mol Endocrinol

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Diabetologia

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Ann Med

Sowers JR

Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab

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et al

Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest

A 74-year-old woman with diabetes

N Engl J Med

Laakso M

Lipids and glucose in type 2 diabetes: What is the cause and effect? Diabetes Care

et al

Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J Clin Invest

Boden G

Effects of free fatty acids on glucose uptake and utilization in healthy women. Diabetes

Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha

Diabetes

Jialal I

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Hyper-insulinemia, hyperglycemia and impaired hemostasis: The Framingham Offspring Study

JAMA

Definition of metabolic syndrome: Report of the National Heart, Lung and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition

Cirulation

Goldfine AB

Inflammation and insulin resistance. J Clin Invest

Spiegelman BM

Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science