The Endoplasmic Reticulum Chaperone Improves Insulin Resistance in Type 2 Diabetes
- 1 March 2005
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 54 (3) , 657-663
- https://doi.org/10.2337/diabetes.54.3.657
Abstract
To determine the role of the endoplasmic reticulum (ER) in diabetes, Akita mice, a mouse model of type 2 diabetes, were mated with either heterozygous knockout mice or two types of transgenic mice of 150-kDa oxygen-regulated protein (ORP150), a molecular chaperone located in the ER. Systemic expression of ORP150 in Akita mice improves insulin intolerance, whereas the exclusive overexpression of ORP150 in pancreatic β-cells of Akita mice did not change their glucose tolerance. Both an insulin tolerance test and hyperinsulinemic-euglycemic clamp revealed that ORP150 enhanced glucose uptake, accompanied by suppression of oxidized protein. Furthermore, ORP150 enhanced the insulin sensitivity of myoblast cells treated with hydrogen peroxide. These data suggest that ORP150 plays an important role in insulin sensitivity and is a potential target for the treatment of diabetes.Keywords
This publication has 36 references indexed in Scilit:
- Adiponectin and Metabolic SyndromeArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative StressPublished by Elsevier ,2003
- A Subset of Chaperones and Folding Enzymes Form Multiprotein Complexes in Endoplasmic Reticulum to Bind Nascent ProteinsMolecular Biology of the Cell, 2002
- Diabetes Mellitus and Exocrine Pancreatic Dysfunction in Perk−/− Mice Reveals a Role for Translational Control in Secretory Cell SurvivalPublished by Elsevier ,2001
- Abundant Expression of 150-kDa Oxygen-Regulated Protein in Mouse Pancreatic Beta Cells Is Correlated with Insulin SecretionBiochemical and Biophysical Research Communications, 2000
- A mutation in the insulin 2 gene induces diabetes with severe pancreatic β-cell dysfunction in the Mody mouseJournal of Clinical Investigation, 1999
- Direct and Indirect Effects of Insulin in Suppressing Glucose Production in Depancreatized Dogs: Role of GlucagonEndocrinology, 1997
- The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscleDiabetes, 1996
- Purification and Characterization of a Novel Stress Protein, the 150-kDa Oxygen-regulated Protein (ORP150), from Cultured Rat Astrocytes and Its Expression in Ischemic Mouse BrainPublished by Elsevier ,1996
- Efficient Regulation of Gene Expression by Adenovirus Vector-Mediated Delivery of the CRE RecombinaseBiochemical and Biophysical Research Communications, 1995