Preclinical developments in type 2 diabetes.
Type 2 diabetes is associated with insulin resistance in peripheral tissues, such as muscle and fat, impaired glucose-stimulated insulin secretion from pancreatic beta-cells and elevated hepatic gluconeogenesis. Current pharmacotherapy does not adequately address the metabolic defects underlying this disease. Thus, novel targets are being explored that enhance insulin action at target tissues, stimulate carbohydrate and fat catabolism, decrease endogenous glucose production and increase pancreatic beta-cell neogenesis and glucose-dependent insulin secretion. This article reviews recent developments in research on several of these targets, namely acetyl-CoA carboxylase 2 (ACC2), I kappa kinase (IKK) beta, dipeptidyl peptidase IV (DPP-IV) and glucagon-like peptide-1 receptor (GLP-1R).
Lenhard
James M
JM
Department of Metabolic Diseases, GlaxoSmithKline Inc, 5 Moore Drive, Research Triangle Park, NC 27709, USA. jml29514@gsk.com
Gottschalk
William K
WK
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D051550:I-kappa B Kinase; D007333:Insulin Resistance; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D018819:Dipeptidyl Peptidase 4; D000103:Acetyl-CoA Carboxylase