[Insulin sensitizer drugs, thiazolidinediones: current state and prospect].
Type 2 diabetes is characterized by decreased secretion of insulin and insulin resistance. Thiazolidinediones are drugs to ameliorate insulin resistance. At present, only pioglitazone is available in Japan. The first drug of this category, troglitazone, has been withdrawn from market because of its liver toxicity in a few patients. The decrease in fasting plasma glucose begins within 2 weeks and reaches the nadir in 8-12 weeks. Plasma insulin levels usually decrease together with plasma glucose. Thiazolidinedione drugs are effective in about 50% of type 2 diabetic patients. The efficacy is higher in patients with obesity, high insulin levels and in aged people and females. The mechanism is thought to be mediated by activation of a nuclear receptor, PPAR-gamma, which is most abundantly expressed in the adipose tissue. Current concept is that, when PPAR-gamma is activated by these drugs, the number of small adipocytes is increased to replace large adipocytes, thereby decreasing the release of TNF-alpha and FFA from adipose tissue. However, there seems to be a complex relationship between the activity of PPAR-gamma and insulin sensitivity. The effect of these new category drugs should be monitored carefully on a long-term basis.
Kuzuya
T
T
Aino Institute for Aging Research, Jichi Medical School.
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003864:Depression, Chemical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D015195:Drug Design; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C089946:2,4-thiazolidinedione