Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in b-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and b-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose -response curves from pregnant rats were shifted to the left in relation to the nonpregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8·3 mM-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2·8 mM-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-a activity in islets from the RP and LPP rats. Protein kinase C (PKC)-a but not phospholipase C (PLC)-b1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. Key words: Glucose homeostasis: Insulin secretion: Malnutrition: Nutritional recovery: PregnancyThe basic mechanism of insulin secretion involves the coupling of glucose metabolism with secondary signals, which maintains insulin release for the duration of elevated blood glucose levels (1) .In rodents, malnutrition during the critical stages of development causes a permanent loss of glucose sensitivity and secretory capacity in pancreatic islets (2) , which is probably the result of alterations to the coupling of stimuli with insulin secretion. In pancreatic islets from rats fed a low-protein (LP) diet during intra-uterine life and/or lactation, reductions in glucokinase (Gck) and hexokinase (Hxk) activity and content (3) , decreases in Ca 2þ uptake and/or Ca 2þ efflux (4) , and impairments in insulin * Corresponding author: M. Q. Latorraca, fax þ55 65 3615 8811, email mqlator@terra.com.br Abbreviations: DG, total area under the glucose curve; DI, total area under the insulin curve; AC3, adenylyl cyclase
Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca] due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.
Adult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway.
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.
Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction.
We assessed the biological value of an okara diet and its effects on the hormonal and metabolic profile of rats submitted to protein restriction during intra-uterine life and lactation and recovered after weaning. Male rats from mothers fed either 17% or 6% protein during pregnancy and lactation were maintained on 17% casein (CC, LC), 17% okara (CO, LO) or 6% casein (LL) diets over 60 d. The nutritional quality of the okara protein was similar to that of casein. The okara diet was effective in the nutritional recovery of rats in growing that were malnourished in early life. Furthermore, the okara diet reversed the hypercholesterolemia and the hepatic steatosis observed in the malnutrition and prevented glucose intolerance in an animal model prone to diabetes mellitus.
BackgroundGap junctions between β-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between β-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1–15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls.ResultsThe low-protein diet reduced the levels of connexin 36 and β-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser279/282]-connexin 43, and it decreased the levels of connexin 36, β-catenin and beta-actin mRNA as well as the levels of connexin 36 and β-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser279/282]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status.ConclusionShort-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion.
Nutritional recovery with a soyabean diet decreases body and fat weights when compared with a casein diet. We investigated whether the reduced adiposity observed in rats recovering from early-life malnutrition with a soyabean diet results from alterations in lipid metabolism in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein during pregnancy and lactation were maintained on 17 % casein (CC and LC groups), 17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The rats maintained on a soyabean diet had similar relative food intakes, but lower body and retroperitoneal WAT weights and a reduced lipid content in the retroperitoneal WAT. The insulin levels were lower in the recovered rats and were elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling protein 1 content in the BAT were decreased in the recovered rats. The thermogenic capacity of the BAT was not affected by the soyabean diet. The lipogenesis rate in the retroperitoneal WAT was similar in all of the groups except for the LL group, which had exacerbated lipogenesis. The enhancement of the lipolysis rate by isoproterenol was decreased in white adipocytes from the soyabean-recovered rats and was elevated in adipocytes from the soyabean-control rats. Thus, in animals maintained on a soyabean diet, the proportions of fat deposits are determined by the lipolysis rate, which differs depending on the previous nutritional status. Key words: Nutritional recovery: Soyabean diet: Adipose tissue: RatsSoya-containing diets have been shown to alter several parameters involved in maintaining body homeostasis, energy expenditure and feeding behaviour (1 -3) . Soya protein and isoflavone have been reported to reduce fat-pad weight by increasing uncoupling protein 1 (UCP-1) expression in brown adipose tissue (BAT) (4) . UCP-1 is a molecule that uncouples mitochondrial oxidative phosphorylation by bypassing the electrochemical gradient across the inner membrane from * Corresponding author: M. S. F. Martins, fax þ55 65 3615 8811, email msfm.cba@gmail.com Abbreviations: BAT, brown adipose tissue; C, control; CC, offspring born to and suckled by mothers fed a control diet that were fed a control diet after weaning; CS, offspring born to and suckled by mothers fed a control diet that were fed a soyabean diet with 17 % protein after weaning; HOMA-IR, homeostasis model assessment of insulin resistance; LC, offspring of mothers fed a low-protein diet that were fed a control diet after weaning; LL, offspring of mothers fed a low-protein diet that were fed a low-protein diet after weaning; LP, low-protein; LS, offspring of mothers fed a low-protein diet that were fed a soyabean diet containing 17 % protein after weaning; RWAT, retroperitoneal white adipose tissue; Tris, 2-amino-2-hydroxymethyl-propane-1,3-diol; UCP-1, uncoupling protein 1; WAT, white adipose tissue.
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