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

Abstract

Summary.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/1, mean_+ SEM p < 0.025), but pretreatment with an oral fat load abolished this effect (plasma GIP: 1008+95 versus 1116+100ng/1, 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/1, p< 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+0.59p~g/1, p<0.01; plasma glucose: 10.2+0.39 versus 8.9 _+ 0.41 mmol/1, p < 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.

Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice

“…In normal subjects (Fig. 5 Left), fat and carbohydrate promote GIP secretion from K cells in the upper portion of the gastrointestinal tract, and this amount of GIP leads to sufficient additional secretion of insulin from the pancreatic ␤ cells to compensate for the insulin resistance, maintaining glucose homeostasis, consistently with previous studies showing elevated GIP levels in human and laboratory animals on a high-fat diet (26,27). It is important to emphasize that high-fat intake can produce both insulin resistance and exaggerated GIP and insulin secretion, synergically creating additional obesity.…”

“…Because fat is a potent GIP secretagogue and plasma GIP levels are elevated under high-fat feeding (26,27), we investigated the pathophysiological role of GIP in these conditions.…”

Gastric inhibitory polypeptide and effects of glycation on glucose transport and metabolism in isolated mouse abdominal muscle

“…These findings are paralleled by observations of Villanueva-Peñacarrillo et al (1994), who found that the other major incretin hormone, tGLP-1, stimulated glycogenic events in rat soleus muscle. Physiological circulating GIP concentrations in the rat range from approximately 5 10 12 to 10 9 mol/l depending on diet (Hampton et al 1983). Our results on the actions of 10 10 and 10 9 mol/l GIP on glucose Figure 2 Effects of 10 8 mol/l insulin and GIP and glycated GIP (10 10 to 10 8 mol/l) on (A) glucose uptake and (B) glucose oxidation in isolated mouse abdominal muscle.…”

Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7–36) amide, on fatty acid synthesis in explants of rat adipose tissue

“…In this study GIP caused a dose-dependent increase in [l4C]acetate incorporation into fatty acids in adi¬ pose tissue over the range 0-5-7-5 ng/ml ( ¬ -50 nmol/1). Physiological circulating GIP levels in the rat range from approximately 0-2 to 4-0 ng/ml (0 5-0-97 nmol/1), depending on the diet (Hampton, Kwasowski, Tan et al 1983), suggesting a possible role for GIP in fatty acid synthesis in vivo. GIP, like insulin, demonstrated the strongest stimulatory effect on fatty acid synthesis in omental adipose tissue.…”