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2 in the modulation of insulin secretion
1 Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa, Italy
2 Department of Oncology, Surgical Unit, University of Pisa, Pisa, Italy
* To whom correspondence should be addressed. E-mail: marchant{at}immr.med.unipi.it.
Peroxisome proliferator-activated receptors (PPARs) are a subgroup of the superfamily of nuclear receptors, with
three distinct main types: 
, 
and 
(subdivided into 1 and 2). Recently, the presence of PPARs- has been
reported in human islets. Whether the other PPARs types can be found in human islets, how islet PPAR- mRNA
expression is regulated by the metabolic milieu, their role in insulin secretion, and the effects of a PPAR- agonist
is not known. In this study, human pancreatic islets were prepared by collagenase digestion and density gradient
purification from non-obese adult donors. The presence of the varying PPARs mRNA was assessed by RT-PCR,
and the effect was evaluated of exposure for up to 24h to either 22.2 mmol/l glucose and/or 0.25, 0.5 or 1.0 mmol/l
long-chain fatty acid mixture (oleate to palmitate, 2 to 1). PPARs- and, to a greater extent, total- and -2 mRNAs
were expressed in human islets, whereas PPAR- mRNA was not detected. Compared to human adipose tissue,
PPARs- mRNA was expressed at lower levels in the islets, and PPARs- at similar levels. The expression of
PPARs -2 mRNA was not affected by exposure to 22.2 mmol/l glucose, whereas it decreased markedly and time-dependently
after exposure to progressively higher FFA. This latter effect was not affected by the concomitant
presence of high glucose. Exposure to FFA caused inhibition of insulin mRNA expression, glucose stimulated
insulin release and reduction of islet insulin content. The PPAR- agonists rosiglitazone and 15-Deoxy-
-
12,14prostaglandin J2 (PGJ2) prevented the cytostatic effect of FFA, as well as the FFA-induced changes of PPAR
and insulin mRNA expression. In conclusion, this study shows that: PPARs- mRNA is expressed in human
pancreatic islets, with predominance of PPARs -2; exposure to FFA down-regulates PPAR-2 and insulin mRNA
expression and inhibits glucose stimulated insulin secretion; exposure to PPARs- agonists can prevent these latter
effects.
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