Influence of a high-fat diet during chronic hyperglycemia oil beta-cell function in pancreatic islet transplants to streptozotocin-diabetic rats

Chronically elevated non-esterified fatty acids (NEFAs) can exert negative effects on beta -cell function both in vitro and in vivo. Negative effects of fatty acids have been difficult to evaluate in overt diabetes because of the attendant hyperglycemia that: gives rise to the confounding influence of 'glucotoxicity', In this work, we tested for the effects of NEFAs in dia betes by (i) taking into account potential effects of prevailing levels of hyperglycemia, and (ii) focusing on lingering (and therefore possibly more serious) effects, A diabetic transplantation model was used in which two is let grafts with 200 and 20 rat islets respectively were transplanted under the kidney capsule of syngeneic recipients previously made diabetic by stre ptozotocin injection. Rats were then fed either a high-fat or a low-fat die t for 7 weeks, followed by 1 week of normal laboratory chow. During dietary intervention, food was consumed ad libitum in one protocol, but was restri cted in the low-fat group in a second protocol (in order to match blood-glu cose levels). A high-fat diet did not affect body weight. At the end of the protocols, graft-bearing kidneys were isolated and perfused. Insulin respo nses to 27.8 mM glucose in perfusion were uniformly absent, in keeping with previously documented effects of chronic hyperglycemia. In contrast, 10 mM arginine induced a marked increase in insulin secretion after a low-fat di et, an effect that was significantly reduced after a high-fat diet (109 +/- 39 vs 13 +/- 15 fmol/min (P < 0.05) and 95 +/- 18 vs 32 +/- 5 fmol/min (P < 0.05) in the 2 protocols respectively). Regardless of protocol, no effect of diet could be detected on graft contents of insulin or preproinsulin mR NA. Thus, under conditions in which influences of chronic hyperglycemia cou ld be accounted for, a previous high-fat diet with elevated NEFAs inhibited arginine-induced insulin secretion: however, the results indicate that ins ulin biosynthesis and/or beta -cell mass were not affected.