Acute and chronic effects of different concentrations of free fatty acids on the insulin secreting function of islets.
BACKGROUND
Lipotoxic effects of free fatty acids (FFAs) on insulin secreting function of islet beta-cells have been demonstrated in recent studies. This toxic effect is especially prominent on postprandial hypertriglyceridemic period. Hypertriglyceridemia and high FFAs levels are the most common metabolic disturbances seen in diabetes mellitus (DM), in particular in uncontrolled cases.


OBJECTIVE
To investigate acute and chronic effects of different concentrations of FFAs on insulin secreting function of pancreas islet beta-cells.


METHODS
We determined the acute and chronic effects of FFAs on insulin secretion dynamics of isolated rat islets. The insulinotropic effects of four D-glucose concentrations (Nil, 5.6, 8.3 and 27.7 mM) were studied in freshly isolated and perifused islets in the presence of two different concentrations (250 micromol/l and 1,250 micromol/l) of three FFAs (palmitate, stearate and oleate) to determine the acute effects. Chronic effects were investigated similarly on islet cells incubated for 72 hours in the presence of nil, 250 micromol/l and 1,250 micromol/l concentrations of FFAs.


RESULTS
There was only a slight increase in insulin secretion at both concentrations of FFAs in freshly isolated islets, and the recovery was complete with a slight decrease in pathologic FFA channel. However, after 72 hour incubation at physiological or higher concentrations of FFAs, insulin secretion was significantly lower, even in the presence of high levels of D-glucose when compared to either nil channel results, or results of the fresh samples. Insulin levels of recovery phase were slightly but significantly lower in physiological and pathologically high FFA conditions when compared to nil condition. In addition, first phase insulin release response was lost in these islets.


CONCLUSIONS
FFAs slightly increased the insulin output of normal fresh pancreas beta-cells. However, chronic exposure to FFAs resulted in loss of first phase insulin release and blunted insulin secretion response to various levels of D-glucose stimulation.
Ayvaz
G
G
Gazi University Faculty of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey. ayvaz@med.gazi.edu.tr
Balos Törüner
F
F
Karakoç
A
A
Yetkin
I
I
Cakir
N
N
Arslan
M
M
D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D019308:Palmitic Acid / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013229:Stearic Acids / Q000494:pharmacology*; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013229:Stearic Acids; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid