Regulation of polyunsaturated fatty acid-stimulated insulin release by GIP in isolated perifused islets.
It has recently been suggested that gastric inhibitory polypeptide (GIP) may block the risk factors associated with both hypo- and hyperglycemia by either suppressing or enhancing (depending on the prevailing glucose conditions) insulin release. In the present study we examined, through the use of isolated perifused murine islets, the effect of GIP on insulin secretion that was stimulated by polyunsaturated fatty acids (PUFA) in the presence of low or high glucose concentrations. For each experiment, islets were preperifused at the rate of 1 ml/min for 1 h at 37 degrees C with Krebs-Ringer bicarbonate buffer pH 7.4 that was continuously gassed with 95%/5%, O2CO2, and which contained 5.5 mM (basal) glucose, 2% bovine albumin, and 100 kIU/ml trasylol. Basal samples were then taken before PUFA were added to the perifusate of 5.5 or 27.7 mM glucose, in the absence (control) or presence of synthetic human GIP, and in 20-min perifusion cycles. Solutions were changed using a stopcock, and effluent samples collected on ice were stored frozen until radioimmunoassay for insulin. The addition of a mixture of 10 mM linoleic acid (18:2, omega 6) and 5 mM linolenic acid (18:3, omega 3), to basal glucose perifusate stimulated insulin secretion from a mean basal rate of 61 +/- 2 to 220 +/- 21 pg/islet/min (p < 0.001, n = 5). When GIP concentrations of either 1 x 10(-9) or 1 x 10(-8) M were added to the fatty acid perifusate, insulin secretion stimulated by PUFA was significantly attenuated in a dose-dependent manner, but was completely restored after withdrawal of GIP.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice
D005231:Fatty Acids, Unsaturated; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide