Insulinotropic potency of lauric acid: a metabolic rationale for medium chain fatty acids (MCF) in TPN formulation.
The need for a better lipid system to satisfy the fuel requirements of patients while avoiding the adverse effects of current systems has led to suggestions that medium chain fatty acids (MCFs) be incorporated into TPN-lipid emulsions. Since clinical situations requiring TPN are associated with metabolic processes mediated by insulin, in the present study we have therefore examined the effects of a variety of medium chain fatty acids on insulin release. Using an isolated perifused mouse islet model, various doses of medium chain fatty acids and the essential fatty acid, linoleic acid, were tested and compared. The possibility of an additive effect of an insulinotropic MCF and linoleate when both are provided together was also examined. Effluent perifusate samples collected on ice during these experiments were assayed for insulin by radioimmunoassay. It was found that the ability of 5 mM of a given MCF to stimulate insulin secretion was dependent upon its chain length. Thus, while adipic acid (C6) had no effect, Caprylic acid (C8) had a minimal effect that was not statistically significant, but capric acid (C10) and lauric acid had very potent effects that were of the same magnitude to the effect of linoleate on insulin secretion. When insulin output was assessed as the mean integrated area under the curve during a 20-min perifusion, 5 mM lauric acid enhanced insulin secretion from a basal 7351 +/- 666 pg to 15,756 +/- 1680 pg (P less than 0.01, n = 5). In the same experiments, 5 mM linoleic acid stimulated insulin release to 11,260 +/- 867 pg (P less than 0.05). When C12 and linoleate were added together, each at a submaximally effective concentration of 2.5 mM, insulin output was 12,712 +/- 1011 pg (P less than 0.05, n = 5), which was not statistically different from the values obtained when the islets were perifused with 5 mM of each fatty acid alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Garfinkel
M
M
Department of Surgery, Duke University Medical School, Durham, North Carolina 27710.
Lee
S
S
Opara
E C
EC
Akwari
O E
OE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007850:Lauric Acids / Q000494:pharmacology*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008297:Male; D051379:Mice; D010289:Parenteral Nutrition, Total
D004338:Drug Combinations; D005227:Fatty Acids; D007328:Insulin; D007850:Lauric Acids; D008041:Linoleic Acids; C030358:lauric acid; D019787:Linoleic Acid