We evaluated the effects of the supplementation with L-glutamine and glutamine dipeptide (GDP) on biochemical and morphophysiological parameters in streptozotocin-diabetic rats. For this purpose, thirty animals were distributed into six groups treated orally (gavage) during thirty days: non diabetic rats (Control) + saline, diabetic + saline; Control + L-glutamine (248 mg/kg), Diabetic + L-glutamine (248 mg/kg), Control + GDP (400 mg/kg), Diabetic + GDP (400 mg/kg). Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg) and confirmed by fasting glucose ≥ 200 mg/dL. Physiological parameters, i.e., body mass, food intake, blood glucose, water intake, urine and faeces were evaluated during supplementation. After the period of supplementation, the animals were euthanized. The blood was collected for biochemical assays (fructosamine, transaminases, lipid profile, total protein, urea, ammonia). Moreover, the jejunum was excised and stored for morphophysiological assays (intestinal enzyme activity, intestinal wall morphology, crypt proliferative index, number of serotoninergic cells from the mucosa, and vipergic neurons from the submucosal tunica). The physiological parameters, protein metabolism and intestinal enzyme activity did not change with the supplementation with L-glutamine or GDP. In diabetic animals, transaminases and fructosamine improved with L-glutamine and GDP supplementations, while the lipid profile improved with L-glutamine. Furthermore, both forms of supplementation promoted changes in jejunal tunicas and wall morphometry of control and diabetic groups, but only L-glutamine promoted maintenance of serotoninergic cells and vipergic neurons populations. On the other hand, control animals showed changes that may indicate negative effects of L-glutamine. Thus, the supplementation with L-glutamine was more efficient for maintaining intestinal morphophysiology and the supplementation with GDP was more efficient to the organism as a whole. Thus, we can conclude that local differences in absorption and metabolism could explain the differences between the supplementation with L-glutamine or GDP.

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

ABSTRACT:The anti-hyperglycemic effect of wood powder of Quassia amara (QA) was evaluated in normal and in alloxan diabetes-induced rats. After a 12 h fast and glycemic check, the animals were orally given 0.9% of saline (control group), metformin (500 mg/kg) or QA (200 mg/kg) and, 30 minutes later, they received an oral glucose dose (1g/kg). The blood glucose level was measured after 30, 60, 90 and 120 minutes. From the oral glucose dose, QA showed anti-hyperglycemic effects, similar to metformin, only in the diabetic animals (p<0.01) when compared to the control group. Although the anti-hyperglycemic mechanism of action of QA was not investigated, a mechanism similar to metformin can be suggested, since both presented similar results for the conditions tested, that is, normal and diabetic rats. It is believed that the use of QA in diabetics could help to control the blood glucose levels and be useful as an alternative therapy.Keywords: alloxan, anti-hyperglicemic effect, diabetes, Quassia amara RESUMO: Efeito anti-hiperglicêmico de Quassia amara (Simaroubaceae) em ratos normais e diabéticos. O efeito anti-hiperglicemiante do pó do lenho de Quassia amara (QA) foi avaliado em ratos normais e diabéticos aloxana induzidos. Após jejum de 12 horas e verificação da glicemia, os animais receberam administração oral de salina 0.9% (grupo controle), metformina (500 mg/kg) ou QA (200 mg/kg) e 30 minutos depois carga oral de glicose (1g/kg). A glicemia foi medida nos próximos 30, 60, 90 e 120 minutos. A partir da carga oral de glicose, a QA mostrou efeito anti-hiperglicemiante, similar a metformina, somente nos animais diabéticos (p<0.01) quando comparados ao grupo controle. Embora o mecanismo de ação anti-hiperglicemiante da QA não tenha sido investigado, podemos sugerir um mecanismo semelhante à metformina, visto que ambos apresentaram resultados similares nas duas condições testadas, ou seja, animais normais e diabéticos. Acredita-se que o uso de QA, em diabéticos, possa auxiliar no controle da glicemia e servir como terapia alternativa. Palavras-chave: aloxana, efeito anti-hiperglicemiante, diabetes, Quassia amaraRev. Bras. Pl. Med., Campinas, v.15, n.3, p.368-372, 2013.

It was previously reported that liver glucose metabolism in rats under caloric restriction differs from that of freely-fed rats. This study hypothesized that these changes (1) were related to the expression of hypothalamic neuropeptides involved in metabolic control, and (2) were not a residual effect of litter size. To those purposes, liver glucose metabolism and hypothalamic expression of the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (agouti gene-related peptide); and of the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaineand amphetamine-related transcripts) were investigated. Male Wistar rats from two different litter sizes (G6 and G12, with 6 or 12 pups, respectively) were subjected to free feeding (GL, ad libitum), 50% caloric restriction (GR) or caloric restriction+ad libitum refeeding (GRL) until the age of 90 days. Biometric values were lower in GR than in GL, while in GRL they were totally or partially recovered. Blood glucose variation during the pyruvate tolerance test (PTT) was small in GR. During in situ liver perfusion, total, basal, and adrenaline-stimulated liver glucose outputs were high in GR, but additional glucose output in the presence of alanine was negligible. Refeeding (GRL) yielded values close to those of GL. Litter size did not consistently influence any of these variables. The expression of transcripts of the hypothalamic neuropeptides was responsive to feeding regimen, litter size and/or their interaction and differed from G6 to G12, while the metabolic changes of the liver were qualitatively equal in both GR. Therefore, the changes in glucose metabolism in the liver of rats under caloric restriction were not determined by either litter size or hypothalamic neuropeptide expression and were linked only to the prevailing feeding regimen of the adult animal.

Early life overfeeding in the rat can be experimentally induced by reducing litter size. This investigation assessed the consequences of this manipulation on glucose metabolism in vivo and in isolated hepatocytes in 150-day old rats. Additionally, after body growth, the effects of caloric restriction and refeeding were tested. Adult rats from control (G9) and reduced litters (G3L) did not differ in body and fat weights, glucose tolerance or insulin resistance (insulin-induced hypoglycemia), or hepatocyte glucose release under basal or gluconeogenic conditions. Caloric restriction (G3R) reduced body and fat weights, decreased glucose decay after insulin injection and decreased hepatocyte gluconeogenic glucose release. Refeeding after caloric restriction reversed these parameters to those of the freely-fed groups (G9 and G3L). Taken together, these results suggest that the liver glucose metabolism is not programmed by lactational overfeeding, but rather is responsive to the current nutritional condition of the animal.