Insulin resistance as the core defect in type 2 diabetes mellitus

Am J Cardiol. 2002 Sep 5;90(5A):3G-10G. doi: 10.1016/s0002-9149(02)02553-5.

Abstract

Insulin resistance is a major contributor to the pathogenesis of type 2 diabetes and plays a key role in associated metabolic abnormalities, such as dyslipidemia and hypertension. Obesity, especially visceral adiposity, is negatively correlated with insulin sensitivity. The release of free fatty acids from adipocytes can block insulin-signaling pathways and lead to insulin resistance. In addition, recently identified adipocyte-specific chemical messengers, the adipocytokines, such as tumor necrosis factor-alpha, adiponectin, and resistin, appear to modulate the underlying insulin resistance. When insulin resistance is combined with beta-cell defects in glucose-stimulated insulin secretion, impaired glucose tolerance, hyperglycemia, or type 2 diabetes can result. The thiazolidinediones are potent peroxisome proliferator-activated receptor-gamma agonists and directly improve insulin resistance and glycemic control in patients with type 2 diabetes. Increasing evidence supports the early use of thiazolidinediones for preventing, delaying, or treating diabetes by improving insulin sensitivity and beta-cell insulin secretion.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / physiology
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism*
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / physiopathology
  • Obesity
  • Risk Factors
  • Thiazoles / pharmacology

Substances

  • Hypoglycemic Agents
  • Insulin
  • Thiazoles