Acute exposure to a precursor of advanced glycation end products induces a dual effect on the rat pancreatic islet function

Abstract

Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine). Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM), MG induced a significant (P < 0.05) increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM), MG significantly inhibited insulin secretion (P < 0.05). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P < 0.05), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P < 0.05). Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells.

Figure 1

Glucose-stimulated insulin secretion (GSIS). Insulinotropic effect of GSIS from isolated pancreatic islets in absence or presence of methylglyoxal. Insulin secretion was stimulated by increasing concentrations of glucose, as indicated below the x-axis. Bars represent the mean ± S.E.M. ^∗ P < 0.01 compared with the respective control group; ^Ω P < 0.01 compared with 5.6 or 16.7 mM of glucose; ^# P < 0.01 compared with 5.6 or 8.3 mM of glucose.

Figure 2

Effect of acetylcholine or epinephrine on GSIS. Insulin secretion was stimulated or inhibited by acetylcholine or epinephrine, as indicated below the x-axis, in absence or presence of methylglyoxal. Bars represent the mean ± S.E.M. of the percentage of insulin release compared with their respective glucose concentrations, which are represented by the line from 0. Ach, 10 μM of acetylcholine in presence of 10 μM of neostigmine + 8.3 mM of glucose; Epi, 1 μM epinephrine + 16.7 mM of glucose. ^Ω P < 0.001 compared with 8.3 mM of glucose; ^# P < 0.001 compared with 16.7 mM of glucose; ^∗ P < 0.05 and ^∗∗ P < 0.001 compared with the respective control group.

Figure 3

Effect of K⁺, forskolin, or leucine on GSIS. Insulin secretion was stimulated or inhibited by K⁺, forskolin, or leucine, as indicated below the x-axis, in absence or presence of methylglyoxal. Bars represent the mean ± S.E.M. of the percentage of insulin release compared with their respective glucose concentrations, which are represented by the line from 0. K⁺, 40 mM of potassium + 5.6 mM of glucose; forskolin, 10 μM of forskolin + 8.3 mM of glucose; leucine, 10 mM of leucine + 5.6 mM of glucose. ^Ψ P < 0.001 compared with 5.6 mM of glucose; ^Ω P < 0.001 compared with 8.3 mM of glucose; ^# P < 0.001 compared with 16.7 mM of glucose; ^∗ P < 0.05 and ^∗∗ P < 0.001 compared with the respective control group.