Insulin resistance as the core defect in type 2 diabetes mellitus.
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.
Goldstein
Barry J
BJ
Department of Medicine, Division of Endocrinology, Diabetes, and Metabolic Disease, Jefferson Medical College, Jefferson Alumni Hall Suite 349, 1020 Locust Street, Philadelphia, PA 19107, USA. barry.goldstein@mail.tju.edu
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D003920:Diabetes Mellitus / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000503:physiopathology; D009765:Obesity; D012307:Risk Factors; D013844:Thiazoles / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles