title: Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet.
abstract: Uncoupling protein 2 (UCP2) may act as an important regulator of insulin secretion. In this study, beta-cell function in UCP2-deficient mice was examined after a 45% high-fat diet (HFD) to assess its role during the development of diet-induced type 2 diabetes. HFD-fed UCP2 (-/-) mice have lower fasting blood glucose and elevated insulin levels when compared with wild-type (WT) mice. UCP2 (-/-) mice also have enhanced beta-cell glucose sensitivity compared with WT mice after HFD, a result that is due in part to the deterioration of glucose responsiveness in WT mice. HFD-fed UCP2 (-/-) mice have increased insulin secretory capacity as a result of increased pancreatic beta-cell mass and insulin content per islet. Islets from WT mice exposed to 0.5 mmol/l palmitate for 48 h have significantly reduced mitochondrial membrane potential, ATP concentrations, and glucose responsiveness compared with UCP2 (-/-) islets, suggesting that elevated UCP2 in WT mice increases proton leak and decreases mitochondrial ATP production. Highly increased carnitine palmitoyl transferase-1 gene expression in UCP2 (-/-) mice is suggestive of enhanced fatty acid oxidizing capacity, particularly after HFD stress. These results further establish UCP2 as a component in glucose sensing and suggest a possible new aspect of UCP2 function during the progression of type 2 diabetes.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Jamie W
authors.initials: JW
authors.lastname: Joseph
authors.forename: Vasilij
authors.initials: V
authors.lastname: Koshkin
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Chan
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D000071246:Uncoupling Protein 2; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D014280:Triglycerides; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D005934:Glucagon