Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet

Abstract

Background: We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon-like peptide-1 (GLP-1).

Objective: Our objective was to combine, in one diet, high levels of fiber and protein to maximize GLP-1 secretion, improve glucose tolerance, and reduce weight gain.

Methods and procedures: Lean (+/?) and obese (cp/cp) male James C Russell corpulent (JCR:LA-cp) rats lacking a functional leptin receptor were fed one of four experimental diets (control, high protein (HP), high fiber (HF, prebiotic fiber inulin), or combination (CB)) for 3 weeks. An oral glucose tolerance test (OGTT) was performed to evaluate plasma GLP-1, insulin and glucose. Plasma lipids and intestinal proglucagon mRNA expression were determined.

Results: Energy intake was lower with the HF diet in lean and obese rats. Weight gain did not differ between diets. Higher colonic proglucagon mRNA in lean rats fed a CB diet was associated with higher GLP-1 secretion during OGTT. The HP diet significantly reduced plasma glucose area under the curve (AUC) during OGTT in obese rats, which reflected both an increased GLP-1 AUC and higher fasting insulin. Diets containing inulin resulted in the lowest plasma triglyceride and total cholesterol levels.

Discussion: Overall, combining HP with HF in the diet increased GLP-1 secretion in response to oral glucose, but did not improve glucose tolerance or lipid profiles more than the HF diet alone did. We also suggest that glycemic and insulinemic response to prebiotics differ among rat models and future research work should examine their role in improving glucose tolerance in diet-induced vs. genetic obesity with overt hyperleptinemia.

Figure 1

Plasma glucagon-like peptide-1 (GLP-1) in response to an oral glucose load in lean and obese rats after the 3-week dietary intervention period. Results represent the mean ± s.e.m. for eight lean rats in each diet group. The left hand panel represents the lean (+/?) rats. Open circles, control diet (C); open squares, high protein (HP); open triangles, high fiber (HF); open diamonds, combination (CB). The CB diet had significantly higher GLP-1 levels vs. the C and HF diet at t = 0, 30 and 60 min (P ≤ 0.05). The insert represents the area under the curve (AUC) for each diet treatment. No significant differences were found in AUC in lean rats. The right hand panel represents the obese (cp/cp) rats. The CB diet had significantly higher fasting GLP-1 levels vs. the HP diet (P ≤ 0.05). For the AUC insert, treatments with different letters are significantly different (P ≤ 0.05).

Figure 2

Plasma insulin in response to an oral glucose load in lean and obese rats. Results represent the mean ± s.e.m. for eight lean rats in each diet group. The left hand panel represents the lean (+/?) rats. Open circles, control diet (C); open squares, high protein (HP); open triangles, high fiber (HF); open diamonds, combination (CB). There were no significant differences between diet groups at time = 0, 30 or 60 min for lean rats. The insert represents the area under the curve (AUC) for each diet treatment. No significant differences were found in AUC for lean rats. The right hand panel represents the obese (cp/cp) rats. At fasting (t = 0), the HP diet had significantly higher insulin levels vs. all other diets (P ≤ 0.05). At t = 60 min the CB diet had significantly lower insulin than the C (P ≤ 0.05). No significant differences were found in AUC for obese rats.

Figure 3

Plasma glucose in response to an oral glucose load in lean and obese rats. Results represent the mean ± s.e.m. for eight lean rats in each diet group. The left hand panel represents the lean (+/?) rats. Open circles, control diet (C); open squares, high protein (HP); open triangles, high fiber (HF); open diamonds, combination (CB). There were no significant differences in plasma glucose between diet treatments in lean rats. Insert represents the area under the curve (AUC) for each diet treatment. No significant differences were found in AUC for lean rats. The right hand panel represents the obese (cp/cp) rats. The CB diet had significantly lower fasting glucose levels compared to the C and HP diet (P ≤ 0.05). For the AUC insert, treatments with different letters are significantly different (P ≤ 0.05).