RGD Reference Report - Functional and molecular defects of pancreatic islets in human type 2 diabetes. - Rat Genome Database

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Functional and molecular defects of pancreatic islets in human type 2 diabetes.

Authors: Del Guerra, S  Lupi, R  Marselli, L  Masini, M  Bugliani, M  Sbrana, S  Torri, S  Pollera, M  Boggi, U  Mosca, F  Del Prato, S  Marchetti, P 
Citation: Del Guerra S, etal., Diabetes. 2005 Mar;54(3):727-35.
RGD ID: 2311306
Pubmed: PMID:15734849   (View Abstract at PubMed)

To shed further light on the primary alterations of insulin secretion in type 2 diabetes and the possible mechanisms involved, we studied several functional and molecular properties of islets isolated from the pancreata of 13 type 2 diabetic and 13 matched nondiabetic cadaveric organ donors. Glucose-stimulated insulin secretion from type 2 diabetic islets was significantly lower than from control islets, whereas arginine- and glibenclamide-stimulated insulin release was less markedly affected. The defects were accompanied by reduced mRNA expression of GLUT1 and -2 and glucokinase and by diminished glucose oxidation. In addition, AMP-activated protein kinase activation was reduced. Furthermore, the expression of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and forkhead box O1 (Foxo-1) was increased. Nitrotyrosine and 8-hydroxy-2'-deoxyguanosine concentrations, markers of oxidative stress, were significantly higher in type 2 diabetic than control islets, and they were correlated with the degree of glucose-stimulated insulin release impairment. Accordingly, 24-h exposure to glutathione significantly improved glucose-stimulated insulin release and decreased nitrotyrosine concentration, with partial recovery of insulin mRNA expression. These results provide direct evidence that the defects of insulin secretion in type 2 diabetic islets are associated with multiple islet cell alterations. Most importantly, the current study shows that the functional impairment of type 2 diabetic islets can be, at least in part, reversible. In this regard, it is suggested that reducing islet cell oxidative stress is a potential target of human type 2 diabetes therapy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IEP 2311306mRNA:increased expression:pancreatic islet (human)RGD 
type 2 diabetes mellitus  ISOPDX1 (Homo sapiens)2311306; 2311306mRNA:increased expression:pancreatic islet (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Mus musculus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Homo sapiens)
PDX1  (pancreatic and duodenal homeobox 1)


Additional Information