Linked Life Data

19213841

Source:http://linkedlifedata.com/resource/pubmed/id/19213841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-21
pubmed:abstractText
GPR39 is a G protein-coupled receptor expressed in liver, gastrointestinal tract, adipose tissue, and pancreas. We have recently shown that young GPR39(-/-) mice have normal body weight, food intake, and fasting glucose and insulin levels. In this study, we examined the role of GPR39 in aging and diet-induced obese mice. Body weight and food intake were similar in wild-type and GPR39(-/-) mice as they aged from 12 to 52 wk or when fed a low-fat/high-sucrose or high-fat/high-sucrose diet. Fifty-two-week-old GPR39(-/-) mice showed a trend toward decreased insulin levels after oral glucose challenge. When fed either a low-fat/high-sucrose or high-fat/high-sucrose diet, GPR39(-/-) mice had increased fed glucose levels and showed decreased serum insulin levels during an oral glucose tolerance test in the face of unchanged insulin tolerance. Pancreas morphology and glucose-stimulated insulin secretion in isolated islets from wild-type and GPR39(-/-) mice were comparable, suggesting that GPR39 is not required for pancreas development or ex vivo insulin secretion. Small interfering RNA-mediated knockdown of GPR39 in clonal NIT-1 beta-cells revealed that GPR39 regulates the expression of insulin receptor substrate-2 and pancreatic and duodenal homeobox-1 in a cell-autonomous manner; insulin receptor substrate-2 mRNA was also significantly decreased in the pancreas of GPR39(-/-) mice. Taken together, our data indicate that GPR39 is required for the increased insulin secretion in vivo under conditions of increased demand, i.e. on development of age-dependent and diet-induced insulin resistance. Thus, GPR39 agonists may have potential for the treatment of type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2586-95
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19213841-Aging, pubmed-meshheading:19213841-Animals, pubmed-meshheading:19213841-Cells, Cultured, pubmed-meshheading:19213841-Dietary Fats, pubmed-meshheading:19213841-Disease Models, Animal, pubmed-meshheading:19213841-Gene Silencing, pubmed-meshheading:19213841-Glucose, pubmed-meshheading:19213841-Homeodomain Proteins, pubmed-meshheading:19213841-Insulin, pubmed-meshheading:19213841-Insulin Receptor Substrate Proteins, pubmed-meshheading:19213841-Insulin Resistance, pubmed-meshheading:19213841-Islets of Langerhans, pubmed-meshheading:19213841-Male, pubmed-meshheading:19213841-Mice, pubmed-meshheading:19213841-Mice, Inbred C57BL, pubmed-meshheading:19213841-Mice, Knockout, pubmed-meshheading:19213841-Obesity, pubmed-meshheading:19213841-RNA Interference, pubmed-meshheading:19213841-Receptors, G-Protein-Coupled, pubmed-meshheading:19213841-Trans-Activators
pubmed:year
2009
pubmed:articleTitle
Disruption of G protein-coupled receptor 39 impairs insulin secretion in vivo.
pubmed:affiliation
Department of Metabolic Diseases,Wyeth Research, Cambridge, Massachusetts 02140, USA.
pubmed:publicationType
Journal Article