A low‐protein diet during pregnancy alters glucose metabolism and insulin secretion

Abstract

In pancreatic islets, glucose metabolism is a key process for insulin secretion, and pregnancy requires an increase in insulin secretion to compensate for the typical insulin resistance at the end of this period. Because a low-protein diet decreases insulin secretion, this type of diet could impair glucose homeostasis, leading to gestational diabetes. In pancreatic islets, we investigated GLUT2, glucokinase and hexokinase expression patterns as well as glucose uptake, utilization and oxidation rates. Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. The insulin secretion in 2.8 mmol l(-1) of glucose was higher in islets from LPP rats than that in islets from CP, CNP and LPNP rats. Maximal insulin release was obtained at 8.3 and 16.7 mmol l(-1) of glucose in LPP and CP groups, respectively. The glucose dose-response curve from LPNP group was shifted to the right in relation to the CNP group. In the CP group, the concentration-response curve to glucose was shifted to the left compared with the CNP group. The LPP groups exhibited an "inverted U-shape" dose-response curve. The alterations in the GLUT2, glucokinase and hexokinase expression patterns neither impaired glucose metabolism nor correlated with glucose islet sensitivity, suggesting that β-cell sensitivity to glucose requires secondary events other than the observed metabolic/molecular events.

Maternal Moderate Physical Training during Pregnancy Attenuates the Effects of a Low-Protein Diet on the Impaired Secretion of Insulin in Rats: Potential Role for Compensation of Insulin Resistance and Preventing Gestational Diabetes Mellitus

“…Herein we showed that maternal low-protein diet induced a reduction in the secretion of insulin. Our results are in accordance with previous studies where maternal low-protein (6% casein) diet induced impairment in the metabolism of glucose and secretion of insulin [1, 35, 36]. It has been suggested that the poor secretory response to glucose observed in islets from low-protein diet rats may be related to a defect in the ability of glucose to increase Ca 2+ uptake and/or to reduce Ca 2+ efflux from β -cells [36] and a reduced islet mass and/orinsulinbiosynthesis [3].…”

“…Here, we demonstrated for the first time that a controlled protocol of physical training before and during gestation increased pancreatic islets glucose-stimulatedinsulinsecretion. This effect was particularly important once maternal protein-restriction has been shown to impair secretion of insulin leading to gestational diabetes as seen in previous study [1]. The underlying mechanism to the effects of maternal physical training on glucose-stimulated insulin secretion remains unknown but can be associated to increased pancreatic β -cell mass by upregulation of growth and survival pathways (AKT, ERK pathways) in pancreatic islets [41].…”

“…Pregnancy requires an increase in insulin secretion-induced glucose metabolism, in order to compensate for the insulin resistance at the end of gestation [1]. In pregnant rats, the threshold of glucose-stimulatedinsulinsecretionbegins to diverge from controls by day 10 and islet cell proliferation and insulinsecretory profiles are inhibited by day 20 to avoid gestational diabetes [2].…”

“…For example, maternal low-protein diet (6% casein) causes a loss of glucose sensitivity and secretory capacity in pancreatic islets, which is probably the result of alterations to the coupling of stimuli with insulin secretion [3]. In fact, a maternal low-protein diet decreases insulin secretion and impairs glucose homeostasis, leading to gestational diabetes mellitus and increased risk of chronic diseases in later life [1, 4]. …”

A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets

“…Interestingly, we previously verified [ 40 ] that islets from rats submitted to protein restriction during pregnancy exhibit an “inverted U-shape” dose–response curve, with elevated basal insulin secretion, a maximal insulin secretion in response to 8.3 mmol/L glucose, and blunted insulin secretion in response to 11.1 and 16.7 mmol/L glucose. It is reasonable to suppose that this secretory profile could, at least in part, to result from alterations in the expression of gap and adherens junction-associated proteins.…”