Fish Oil Affects Pancreatic Fat Storage, Pyruvate Dehydrogenase Complex Activity and Insulin Secretion in Rats Fed a Sucrose-Rich Diet

Abstract

Rats fed a sucrose-rich diet (SRD) develop hypertriglyceridemia and a marked decline in beta cell function. The purpose of this study was to determine whether changes in triglyceride concentration and/or altered pyruvate dehydrogenase complex (PDHc) activity contribute to the beta cell dysfunction, and to analyze the effect of dietary fish oil on the altered patterns of insulin secretion and peripheral insulin resistance. Rats were fed an SRD for 210 d. One-half of the rats continued consuming the SRD until d 270. The other half received an SRD in which fish oil (FO) was partially substituted for corn oil until d 270. A group of rats was fed a control diet (CD) throughout the experiment. The islets of rats fed the SRD had a greater triglyceride concentration and lower PDHc activity than those fed the CD. Insulin secretion patterns under the stimulus of glucose, palmitate or L-arginine were impaired in SRD-fed compared with CD-fed rats. This was accompanied by peripheral insulin resistance, mild hyperglycemia, a sharp increase of plasma triglyceride and free fatty acid levels and greater epididymal and retroperitoneal fat weights. FO normalized and/or improved these variables. Our results indicate that the increased fat storage and decreased PDHc activity in the beta cells play a key role in the abnormal insulin secretion of rats chronically fed an SRD. This is consistent with the reversion of these alterations by dietary FO.

Islet neogenesis: an apparent key component of long-term pancreas adaptation to increased insulin demand

“…This effect could be partly ascribed to a change in the hexokinase:glucokinase ratio of islet cells (Leahy 1996, Massa et al 2001, resulting in increased islet glucose metabolism (Massa et al 2001). These results agree with the significantly higher second phase of insulin released by perifused islets in response to glucose reported in this animal model, as reported by Pighin et al (2003). As described in that report, while insulin secretion in vitro was higher in SRD6 rats than in CD rats, their serum insulin levels were not.…”

“…As described in that report, while insulin secretion in vitro was higher in SRD6 rats than in CD rats, their serum insulin levels were not. This apparent discrepancy between in vitro and in vivo results could be ascribed to the inhibitory effect of high levels of circulating fatty acids reported by our group (Pighin et al 2003) and other authors as well (Zhou & Grill 1995, Chen & Reaven 1999. Consequently, the circulating levels of insulin in SRD6 rats were insufficient to cope with the increased peripheral demand of insulin, since these animals had significantly higher serum glucose and triacylglycerol levels than CD rats.…”

“…The moderate hyperglycaemia present in our rats and the altered glucose oxidation (decreased activity of the PDHc complex) recently reported in the same experimental model (Pighin et al 2003) could represent an additional factor limiting the functional and morphological pancreas reaction. In fact, hyperglycaemia can impair the secretion of insulin (Leahy et al 1986, Rossetti et al 1987, Portha et al 1988, Leahy 1996, Deng et al 2004, the rate of -cell replication and the degree of islet neogenesis (Maedler et al 2001).…”

“…Islets isolated from these rats have a normal insulin content (Lombardo et al 1996, Del Zotto et al 2002, but their secretion pattern is characterized by the absence of the first peak and the enhancement of the second phase of insulin release in response to glucose , Pighin et al 2003. Islets from rats fed SRD for 9 months also had an increased content of triglyceride and reduced pyruvate dehydrogenase complex activity (PDHc) (Pighin et al 2003). All these characteristics resemble those found in people with type 2 diabetes (Polonsky et al 1996, Clark et al 2001, Weir et al 2001, Deng et al 2004.…”

The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n−3 fatty acids with glucose metabolism

“…Potential mechanisms by which marine nÀ3 fatty acids could beneficially affect glucose metabolism include lowering of circulating triacylglycerol and FFA concentrations (Pighin et al, 2003), and of intramuscular lipids (Jucker et al, 1999). The inverse associations of EPA and DHA intake with 2-h serum FFA in women of the present study are compatible with such a FFA-lowering effect of these fatty acids.…”