L-glutamine and whole protein restore first-phase insulin response and increase glucagon-like peptide-1 in type 2 diabetes patients

Abstract

L-glutamine triggers glucagon-like peptide-1 (GLP-1) release from L cells in vitro and when ingested pre-meal, decreases postprandial glycaemia and increases circulating insulin and GLP-1 in type 2 diabetes (T2D) patients. We aimed to evaluate the effect of oral L-glutamine, compared with whole protein low in glutamine, on insulin response in well-controlled T2D patients. In a randomized study with a crossover design, T2D patients (n = 10, 6 men) aged 65.1 ± 5.8, with glycosylated hemoglobin (HbA1c) 6.6% ± 0.7% (48 ± 8 mmol/mol), received oral L-glutamine (25 g), protein (25 g) or water, followed by an intravenous glucose bolus (0.3 g/kg) and hyperglycemic glucose clamp for 2 h. Blood was frequently collected for analyses of glucose, serum insulin and plasma total and active GLP-1 and area under the curve of glucose, insulin, total and active GLP-1 excursions calculated. Treatments were tested 1-2 weeks apart. Both L-glutamine and protein increased first-phase insulin response (p ≤ 0.02). Protein (p = 0.05), but not L-glutamine (p = 0.2), increased second-phase insulin response. Total GLP-1 was increased by both L-glutamine and protein (p ≤ 0.02). We conclude that oral L-glutamine and whole protein are similarly effective in restoring first-phase insulin response in T2D patients. Larger studies are required to further investigate the utility of similar approaches in improving insulin response in diabetes.

Figures

Figure 1

The effect of l-glutamine (Gln), protein or water on blood glucose (A and B), serum insulin (C; first-phase insulin response, inset, and D) and plasma total (E and F) and active (G and H) GLP-1 excursions and area under the curve (AUC), respectively in response to intravenous glucose bolus and hyperglycemic glucose clamp. AUC of the response of glucose, insulin and total and active GLP-1 at t = 0–30 min (30 min post treatment ingestion), t = 30–40 min (10 min post glucose injection) and t = 40–150 min (during hyperglycemic glucose clamp) were calculated and differences between treatments tested by one-way ANOVA with Tukey posthoc analyses. Data are mean ± SEM. Horizontal lines above AUC bars indicate statistical significance (p ≤ 0.05).

Figure 1

The effect of l-glutamine (Gln), protein or water on blood glucose (A and B), serum insulin (C; first-phase insulin response, inset, and D) and plasma total (E and F) and active (G and H) GLP-1 excursions and area under the curve (AUC), respectively in response to intravenous glucose bolus and hyperglycemic glucose clamp. AUC of the response of glucose, insulin and total and active GLP-1 at t = 0–30 min (30 min post treatment ingestion), t = 30–40 min (10 min post glucose injection) and t = 40–150 min (during hyperglycemic glucose clamp) were calculated and differences between treatments tested by one-way ANOVA with Tukey posthoc analyses. Data are mean ± SEM. Horizontal lines above AUC bars indicate statistical significance (p ≤ 0.05).