[Future targets in the treatment of type 2 diabetes].
Prevention and treatment of type 2 diabetes mellitus (T2DM) and the metabolic syndrome represent a major clinical challenge, because effective strategies such as fat restriction and exercise are difficult to implement into diabetes treatment. Based on the increasing knowledge on the pathogenesis of T2DM, new therapeutic approaches are currently under investigation. Potential targets of new therapeutic approaches include: (i) Inhibition of hepatic glucose production, (ii) stimulation of glucose-dependent insulin secretion, (iii) enhancement of insulin signal transduction, and (iv) reduction of body fat mass. Agonists of glucagon-like-peptide 1 (GLP-1) and antagonists of dipeptidylpeptidase IV, which inactivates GLP-1, stimulate glucose-dependent insulin secretion, improve hyperglycemia and are already tested in clinical trials. In humans, glucagon antagonists and an amylin analogue reduce glucagon-dependent glucose production. The glucose-lowering effect of current modulators of lipid oxidation is not pronounced and their use could be limited by side effects. In addition to clinically approved thiazolidendiones, new agonists of the peroxisome proliferator activator receptor gamma (PPAR gamma) as well as combined PPAR alpha/gamma agonists are developed at present. The direct modulation of insulin signal transduction is still limited to experimental studies.
Stingl
Harald
H
Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Osterreich.
Roden
Michael
M
D000818:Animals; D002986:Clinical Trials as Topic; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors; D005544:Forecasting; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D015227:Lipid Peroxidation; D024821:Metabolic Syndrome / Q000378:metabolism / Q000628:therapy; D051379:Mice; D010078:Oxazines / Q000627:therapeutic use; D010446:Peptide Fragments / Q000627:therapeutic use; D010666:Phenylpropionates / Q000627:therapeutic use; D011498:Protein Precursors / Q000627:therapeutic use; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000627:therapeutic use; D014157:Transcription Factors / Q000378:metabolism
D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006442:Glycated Hemoglobin; D038362:Glycogen Synthase Kinase 3; D007004:Hypoglycemic Agents; D007328:Insulin; D010078:Oxazines; D010446:Peptide Fragments; D010666:Phenylpropionates; D011498:Protein Precursors; D011972:Receptor, Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014157:Transcription Factors; C432703:ragaglitazar