Pancreatic islet response to hyperglycemia is dependent on peroxisome proliferator-activated receptor alpha (PPARalpha).
This study tests the hypothesis that islet peroxisome proliferator-activated receptor alpha (PPARalpha) influences insulin secretion. Freshly isolated islets of normoglycemic PPARalpha-null mice display no major alteration of glucose-stimulated insulin release. However, after 24 h of culture in high glucose, PPARalpha-null islets exhibit elevated basal insulin secretion and fail to increase insulin mRNA. 24-h culture with palmitate replicates this phenotype in wild-type islets. The data suggest that PPARalpha is needed to ensure appropriate insulin secretory response in situation of short-term hyperglycemia, likely by maintaining islet lipid homeostasis. As such, islet PPARalpha could contribute to delay the progression of type 2 diabetes.
Bihan
Hélène
H
INSERM U 341, Hôtel-Dieu, Paris, France.
Rouault
Christine
C
Reach
Gérard
G
Poitout
Vincent
V
Staels
Bart
B
Guerre-Millo
Michèle
M
D000821:Animal Feed; D000818:Animals; D005223:Fats / Q000494:pharmacology; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques
D005223:Fats; D007328:Insulin; D047493:PPAR alpha; D005947:Glucose