Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal function in young animals is influenced by maternal factors, such as alterations in the maternal diet. Glucagon-like peptide 2 (GLP-2) enhances intestinal growth and absorption in mature animals. Glucocorticosteroids induce intestinal maturation in neonates and increase sugar uptake in adult animals. It is not known if maternally administered GLP-2 or glucocorticosteroids have persistent effects on intestinal transport in the offspring. This study was undertaken to determine (1) the influence of maternal GLP-2, dexamethasone (DEX) and GLP-2+DEX on intestinal sugar uptake in postweaning offspring and (2) if alterations in uptake are due to variations in intestinal morphology, sugar transporter abundance or the abundance of selected signals. Nursing rat dams were treated during pregnancy and lactation with GLP-2 (0.1 mug/g per day sc), DEX (0.128 microg/g per day sc), GLP-2+DEX or placebo. The offspring were sacrificed 4 weeks after weaning, and glucose and fructose uptake was determined using an in vitro intestinal ring uptake technique. sodium-dependent glucose transporter, glucose transporter (GLUT) 5, GLUT2, sodium potassium adenosine triphosphatase and selected signals were assessed by immunohistochemistry. The treatments did not affect body weights or intestinal morphology. GLP-2 and GLP-2+DEX increased jejunal fructose uptake, and GLP-2+DEX increased the jejunal and ileal maximal transport rate for glucose uptake. Protein kinase B and mammalian target of rapamycin abundance were also increased, while transporter abundance was unchanged. We speculate that these alterations in sugar uptake may be due to changes in the intrinsic activity of the transporters mediated by the phosphatidylinositol-3-kinase pathway. These alterations in uptake may have nutritional implications for the offspring of mothers who may be treated with GLP-2 or glucocorticosteroids.
 ...
PMID:Dexamethasone and GLP-2 administered to rat dams during pregnancy and lactation have late effects on intestinal sugar transport in their postweaning offspring. 1765 62

During type 1 diabetes, most beta cells die by immune processes. However, the precise fate and characteristics of beta cells and islet autoimmunity after onset are unclear. Here, the extent of beta cell survival was determined in the non-obese diabetic (NOD) mouse during increasing duration of disease and correlated with insulitis. Pancreata from female NOD mice at diagnosis and at 1, 2, 3 and 4 weeks thereafter were analysed immunohistochemically for insulin, glucagon and somatostatin cells and glucose transporter-2 (glut2) and correlated with the degree of insulitis and islet immune cell phenotypes. Insulitis, although variable, persisted after diabetes and declined with increasing duration of disease. During this period, beta cells also declined sharply whereas glucagon and somatostatin cells increased, with occasional islet cells co-expressing insulin and glucagon. Glut2 was absent in insulin-containing cells from 1 week onwards. CD4 and CD8 T cells and macrophages persisted until 4 weeks, in islets with residual beta cells or extensive insulitis. We conclude that after diabetes onset, some beta cells survive for extended periods, with continuing autoimmunity and expansion of glucagon and somatostatin cells. The absence of glut2 in several insulin-positive cells suggests that some beta cells may be unresponsive to glucose.
 ...
PMID:Presence of residual beta cells and co-existing islet autoimmunity in the NOD mouse during longstanding diabetes: a combined histochemical and immunohistochemical study. 1789 62

Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I mRNA, and ileal proglucagon mRNA. Plasma IGF-I concentration was restored to fed levels with 2 days of ad libitum refeeding but not with 4 days of intravenous or intragastric refeeding. Administration of an inhibitor of endogenous GLP-2 (rat GLP-2 3-33) during ad libitum refeeding partially attenuated mucosal growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas intravenous refeeding had no effect. Intestinal regeneration after 4 days of intragastric or 2 days of ad libitum refeeding was positively associated with increases in plasma concentrations of GLP-2 and jejunal IGF-I mRNA. These data suggest that luminal nutrients stimulate intestinal growth, in part, by increased expression of both GLP-2 and IGF-I.
 ...
PMID:Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats. 1825 35

Intestinal glucose absorption comprises two components. One is classical active absorption mediated by the Na+/glucose cotransporter. The other is a diffusive component, formerly attributed to paracellular flow. Recent evidence, however, indicates that the diffusive component is mediated by the transient insertion of glucose transporter type 2 (GLUT2) into the apical membrane. This apical GLUT2 pathway of intestinal sugar absorption is present in species from insect to human, providing a major route at high sugar concentrations. The pathway is regulated by rapid trafficking of GLUT2 to the apical membrane induced by glucose during assimilation of a meal. Apical GLUT2 is therefore a target for multiple short-term and long-term nutrient-sensing mechanisms. These include regulation by a newly recognized pathway of calcium absorption through the nonclassical neuroendocrine l-type channel Cav1.3 operating during digestion, activation of intestinal sweet taste receptors by natural sugars and artificial sweeteners, paracrine and endocrine hormones, especially insulin and GLP-2, and stress. Permanent apical GLUT2, resulting in increased sugar absorption, is a characteristic of experimental diabetes and of insulin-resistant states induced by fructose and fat. The nutritional consequences of apical and basolateral GLUT2 regulation are discussed in the context of Western diet, processed foods containing artificial sweeteners, obesity, and diabetes.
 ...
PMID:Sugar absorption in the intestine: the role of GLUT2. 1839 59

A major, yet poorly understood, feature of type 2 diabetes is the excessive hepatic glucose production and the corresponding insulin resistance leading to fasting hyperglycaemia. The tremendous amount of work done to provide the physiological and molecular mechanisms explaining this impairment has led to the emergence of several consensual hypotheses. Among these, is the increased daily and unregulated plasma glucagon concentration in type 2 diabetic patients. Therefore, studies aiming to understand the physiological regulation of glucagon secretion and the corresponding impairment during diabetes are directly relevant to the treatment of type 2 diabetes. Glucagon secretion by alpha-cells is an immediate response to glucopenia. Abnormal secretion of glucagon and other counterregulatory hormones is a hallmark of type 1 and type 2 diabetes and a major limitation to the use of strong hypoglycaemia agents. A few molecular mechanisms of glucose detection triggering counterregulation and in particular inducing glucagon secretion or suppressing it during hyperglycaemic episodes, have been identified. Such mechanisms are related to those of the insulin secreted beta-cell. The glucose transporter GLUT2 and the K-ATP dependent channel, as well as regulatory mechanisms, involved the central nervous system and the gut-brain hormone GLP-1. Over the last years, glucoincretins have provided promising results for the normalization of plasma glucagon concentration of type 2 diabetic patients, which could partly explain the therapeutic benefits of incretin-related therapy. The underlined mechanisms of GLP-1 regulated glucagon secretion are most likely related to the action of the hormone on the activation of the portal and brain glucose sensors. Certainly, strategies aiming to restore glucose-regulated glucagon secretion are important milestones for the treatment of diabetic patient and the prevention of iatrogenic hypoglycaemia.
 ...
PMID:Pancreatic alpha-cell dysfunction in diabetes. 1864 May 86

Fish oil treatment was used in reversing the morphological and metabolic changes of C57BL/6 mice fed high-fat-high-sucrose (HFHS) diet. Two-month-old male C57BL/6 mice were fed HFHS chow or standard chow (SC). At 3 months of age, HFHS mice were separated into an untreated group (HFHS) and a group treated with fish oil (HFHS-Fo, 1.5g/kg/day). At 4 months of age, HFHS fed mice had an increase in body mass (BM) and total body fat, when the animals were sacrificed. Both parameters were lower in HFHS-Fo than in HFHS mice. Plasma glucose and insulin levels were not affected among the groups, but HFHS and HFHS-Fo animals had higher homeostasis model assessment for insulin resistance HOMA-IR ratio. HFHS and HFHS-FO mice had increased plasma total cholesterol and LDL-C, HFHS-Fo increased plasma HDL-C and decreased triglycerides levels. The liver mass (LM) and the adipocytes' size were larger in HFHS mice, while HFHS-Fo mice had a lower LM and smaller adipocytes. The liver steatosis and hepatocyte binucleation were increased in HFHS mice, while HFHS-Fo mice had reduced liver steatosis and hepatocyte binucleation. HFHS-Fo mice had a lower pancreas mass, while HFHS animals had higher islet pancreatic diameter. The SC group showed strong expression for insulin, glucagon and a glucose transporter type 2 GLUT-2 in all pancreatic islets, while in HFHS mice there was less expression for GLUT-2. However, HFHS-Fo mice showed an increase of GLUT-2 expression. In conclusion, dietary fish oil treatment reduces body mass and fat pad adiposity, and also by reducing plasma TG and pancreatic islet hypertrophy in mice fed high-fat-high-sucrose diet. Furthermore, fish oil improves glucagon and GLUT-2 expressions when it is decreased in insulin, but in hepatocyte binucleation and hepatic steatosis where the effect is reduced.
 ...
PMID:Adipose tissue, liver and pancreas structural alterations in C57BL/6 mice fed high-fat-high-sucrose diet supplemented with fish oil (n-3 fatty acid rich oil). 1918 42

Elevated liver fat content occurs in high-yielding dairy cows during the transition from pregnancy to lactation after fat mobilization and may affect hepatic glucose metabolism, but the degree of liver fat storage is highly variable. Therefore, we studied metabolic and endocrine changes and hepatic glucose metabolism in cows that markedly differ in liver fat content. Multiparous cows from the same herd with high (HFL; n = 10) and low (LFL; n = 10) liver fat contents (mean of d 1, 10, and 21 after calving for each cow, respectively) were studied from 60 d before expected calving to 56 d in milk. Cows were fed ad libitum and all cows received the same diets. Liver samples were taken on d 1, 10, and 21 after calving; mean fat content (+/-SEM) in liver of HFL cows was 174 +/- 9.6 mg/g, whereas mean liver fat content in LFL cows was 77 +/- 3.3 mg/g. Blood samples were taken 20 and 7 d before expected calving and 0, 7, 14, 28, and 56 d after calving to measure plasma concentrations of nonesterified fatty acids, beta-hydroxybutyrate, glucose, insulin, glucagon, insulin-like growth factor-I, and leptin. In liver, glycogen content as well as mRNA levels of phosphoenolpyruvate carboxykinase, pyruvate carboxylase, glucose-6-phosphatase, and glucose transporter were measured by quantitative real-time PCR. Back fat thickness decreased and dry matter intake increased with onset of lactation, and back fat thickness was higher but dry matter intake was lower in HFL than in LFL. Energy-corrected milk yield did not differ between groups, but milk fat content was higher and lactose content was lower in HFL than LFL at the beginning of lactation. Energy balance was more negative in HFL than in LFL. Plasma nonesterified fatty acids and beta-hydroxybutyrate concentrations increased and plasma glucose concentration tended to decrease more in HFL than LFL with onset of lactation. Glucagon to insulin ratios increased more in HFL than LFL with onset of lactation. Hepatic glycogen content was higher in LFL than HFL, whereas mRNA levels of glucose-6-phosphatase and pyruvate carboxylase were higher in HFL than in LFL, and cytosolic phosphoenolpyruvate carboxykinase mRNA level increased similarly after parturition in both groups. In conclusion, an elevated liver fat content was related to greater fat mobilization and reduced feed intake and was associated with effects on hepatic glucose metabolism. As environment and feeding management were the same, individual cow factors were responsible for differences in energy metabolism during the transition period.
 ...
PMID:Performance and metabolic and endocrine changes with emphasis on glucose metabolism in high-yielding dairy cows with high and low fat content in liver after calving. 1930 36

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.
 ...
PMID:Olive oil consumption and non-alcoholic fatty liver disease. 1937 Jul 76

Numerous studies conducted in a diversity of adult tissues have shown that certain stem cells are characterized by the expression of a protein known as the ABCG2 transporter (where ABC is ATP- binding cassette). In the adult pancreas, although various multipotent progenitors have been proposed, the ABCG2 marker has only been detected in the so-called 'side population' (a primitive haematopoietic cell population with a multipotential capacity). In the present study we sought to identify new ABCG2+ pancreatic cell populations and to explore whether they exhibit the properties of progenitor cells. We isolated and expanded mitoxantrone-resistant cells from pancreata of lactating rats by drug selection. These cells were characterized and maintained in different stages of differentiation using several media 'cocktails' plus Matrigel (BD Biosciences). Differentiation was assessed by RT-PCR (reverse transcription-PCR), immunocytochemistry, electron microscopy and ELISA. The expanded cell population demonstrated a phenotype of PaSCs (pancreatic stellate cells). Spontaneous cell clusters occurred during cell expansion and they showed weak expression of the transcription factor Pdx1 (pancreatic and duodenal homeobox 1). Moreover, the presence of inductive factors in the Matrigel plus exendin-4 led to an increase in Pdx1 and endocrine genes, such as insulin, islet amyloid polypeptide, glucagon, the glucose transporter GLUT2, chromogranin A and the convertases PC1/3 and PC2 were also detected. Immunocytochemical analysis showed co-localization of insulin and C-peptide, whereas ultrastructural studies revealed the presence of granules. Insulin secretion from cell clusters was detected in the cell culture medium. We identified a population of PaSCs that express the ABCG2+ transporter and have the capacity to transdifferentiate into insulin-producing cells. Although the potential therapeutic application remains to be tested, PaSCs could represent a future option for insulin replacement in diabetes research.
 ...
PMID:Identification of a pancreatic stellate cell population with properties of progenitor cells: new role for stellate cells in the pancreas. 1955 23

Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM.
 ...
PMID:Insulin-producing cells derived from rat bone marrow and their autologous transplantation in the duodenal wall for treating diabetes. 1938 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>