Document Detail


The permissive effects of glucose on receptor-operated potentiation of insulin secretion from mouse islets: a role for ERK1/2 activation and cytoskeletal remodelling.
MedLine Citation:
PMID:  23344729     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: Glucose plays two distinct roles in regulating insulin secretion from beta cells-an initiatory role, and a permissive role enabling receptor-operated secretagogues to potentiate glucose-induced insulin secretion. The molecular mechanisms underlying the permissive effects of glucose on receptor-operated insulin secretion remain uncertain. We have investigated the role of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and consequent cytoskeletal remodelling in this process. METHODS: Insulin release was measured from groups of isolated mouse islets using static incubation experiments and subsequent radioimmunoassay of samples. ERK1/2 activation was measured by western blotting of islet protein samples for both phosphorylated and total ERK1/2. Rhodamine-phalloidin staining was used to measure filamentous actin in dispersed primary beta cells. RESULTS: Inhibition of ERK1/2 blocked potentiation of glucose-induced insulin release by the receptor-operated secretagogues kisspeptin, A568, exendin-4 and JWH015, although the agonists alone had minimal effects on ERK1/2 activation, suggesting a permissive rather than causal role for ERK1/2 activation in receptor-operated insulin release. Following pharmacological activation of ERK1/2 all agonists caused a significant increase in insulin release from islets incubated with sub-stimulatory levels of glucose. ERK1/2 inhibition significantly reduced the glucose-dependent decreases in filamentous actin observed in primary beta cells, while pharmacological dissociation of actin filaments enabled all receptor-operated secretagogues tested to significantly stimulate insulin release from islets at a sub-stimulatory glucose concentration. CONCLUSIONS/INTERPRETATION: Glucose-induced ERK1/2 activation in beta cells mediates the permissive effects of stimulatory glucose concentrations on receptor-operated insulin secretagogues, at least in part through effects on actin depolymerisation and cytoskeletal remodelling.
Authors:
J E Bowe; A Chander; B Liu; S J Persaud; P M Jones
Related Documents :
24469589 - Self-reported discrimination, diabetes distress, and continuous blood glucose in women ...
23948059 - Flavonoids from tetrastigma obtectum enhancing glucose consumption in insulin-resistanc...
21436719 - Intensive insulin treatment attenuates burn-initiated acute lung injury in rats: role o...
10994449 - Modified grid pattern treatment of diabetic perifoveal edema by orange dye laser photoc...
18474939 - Connective tissue growth factor is necessary for retinal capillary basal lamina thicken...
24583859 - Chronic administration of bovine milk-derived α-lactalbumin improves glucose tolerance...
17068109 - Insulin sensitivity in streptozotocin-induced diabetic rats treated with different dose...
24431769 - Type 2 diabetes and edentulism as chronic co-morbid factors affecting indian elderly: a...
11728949 - Platelet collagen receptor alpha2beta1 integrin and glycoprotein iiia pl(a1/a2) polymor...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetologia     Volume:  -     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Diabetes Research Group, Division of Diabetes and Nutritional Sciences, Hodgkin Building, King's College London, London, SE1 1UL, UK, james.bowe@kcl.ac.uk.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and...
Next Document:  Previous maternal infection protects offspring from enterovirus infection and prevents experimental ...