Effect of pretreatment with a high fat diet on the gastric inhibitory polypeptide and insulin responses to oral triolein and glucose in rats.

Male Wistar rats were pretreated with 3 ml triolein orally for 4 days in addition to their normal diet. A similar control group were allowed free access to normal laboratory food. When given an oral fat load (1 ml triolein) plasma gastric inhibitory polypeptide (GIP) and triglyceride levels were significantly higher in the fat pretreated group. Inhibition of fat-stimulated GIP release by exogenous insulin was demonstrated in the untreated control group (plasma GIP: 663 +/- 49 versus 853 +/- 92 ng/l, mean +/- SEM p less than 0.025), but pretreatment with an oral fat load abolished this effect (plasma GIP: 1008 +/- 95 versus 1116 +/- 100 ng/l, p NS). Plasma glucose levels were significantly higher in fat pretreated rats given oral fat and intraperitoneal insulin compared with untreated controls (plasma glucose nadir 2.6 +/- 0.48 versus 1.6 +/- 0.15 mmol/l, p less than 0.05). Fat-pretreated rats showed significantly higher insulin and glucose levels compared with the untreated rats when given oral glucose (plasma insulin: 6.2 +/- 1.2 versus 2.5 +/- 0.59 micrograms/l, p less than 0.01; plasma glucose: 10.2 +/- 0.39 versus 8.9 +/- 0.41 mmol/l, p less than 0.025). Pretreatment of rats on a high fat diet causes (1) increased GIP secretion in response to an oral fat load, (2) abolition of the feed-back inhibition of exogenous insulin on fat-stimulated GIP release, and (3) some degree of insulin resistance.