Biosynthesis of two stage-specific membrane proteins during transformation of Plasmodium gallinaceum zygotes into ookinetes

We have studied the synthesis and expression of surface proteins in zygotes of Plasmodium gallinaceum during their transformation to mature ookinetes. The cells were biosynthetically labelled in vitro using [35S]methionine and proteins were immunoprecipitated with rabbit anti-ookinete serum or monoclonal antibodies. Early zygotes (approx. 2 h post-gametogenesis and fertilization) synthesized and expressed on their surface a protein of Mr 26 000 as observed under reducing conditions on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) (31 000 under non-reducing conditions) and continued to do so for 8-10 h; thereafter synthesis of the Mr 26 000 protein declined and little or none was synthesized in the mature ookinetes (greater than 20 h post-gametogenesis). Between 3-5 h post-gametogenesis, zygotes also began to synthesize a protein of Mr 28 000 (34 000 under non-reducing conditions). Synthesis and expression of this surface protein continued throughout development; and the Mr 28 000 protein was the predominant surface protein synthesized by the mature ookinete. Mr 26 000 and Mr 28 000 proteins have been designated earlier as PgO-1 and PgO-2 respectively (Carter and Kaushal, Mol. Biochem. Parasitol. (1984) 13, 235-241). Neither protein was synthesized in the gametocytes prior to gametogenesis. Both proteins could be labelled with [3H]glucosamine or [3H]mannose. When zygotes were incubated with [3H]palmitic acid both PgO-1 and PgO-2 bound fatty acids in covalent linkage. The two proteins do not otherwise appear to be structurally related. They were differentially immunoprecipitated by different monoclonal antibodies and gave rise to distinct patterns of peptides following digestion with proteases such as Staphylococcus aureus V-8, trypsin and chymotrypsin.     

Identifying undiagnosed diabetes: cross-sectional survey of 3.6 million patients' electronic records.

BACKGROUND: Around 1% of the UK population has diabetes that is either undiagnosed or unrecorded on practice disease registers. AIM: To estimate the number of people in UK primary care databases with biochemical evidence of undiagnosed diabetes. To develop simple practice-based search techniques to support early recognition of diabetes. DESIGN OF STUDY: Cross-sectional survey of 3 630 296 electronic records. SETTING: Four hundred and eighty UK practices contributing to the QRESEARCH database. METHOD: Electronic searches to identify people with no diabetes diagnosis in one of two categories (A and B), using the most recently recorded blood glucose measurement: random blood glucose level >or=11.1 mmol/l or fasting blood glucose level >or=7.0 mmol/l (A); either a random or a fasting blood glucose level >or=7.0 mmol/l (B). An additional outcome measure was the proportion of the population with at least one blood glucose measurement in the record. RESULTS: The number (percentage) identified in category A was 3758 (0.10% of the total population); the number in category B was 32 785 (0.90%). Projected to a practice of 7000 patients, around eight patients have biochemical evidence of undiagnosed diabetes, and 68 have results suggesting the need for further follow-up. One-third of people aged over 40 years without diabetes have a blood glucose measurement in the past 2 years in their record. CONCLUSION: People with possible undiagnosed diabetes are readily identifiable in UK primary care databases through electronic searches using blood glucose data. People with borderline levels, who may benefit from interventions to reduce their risk of progression to diabetes, can also be identified using practice-based software.     

The effect of a 1-deoxynojirimycin derivative on post-prandial blood glucose and insulin levels in healthy black and white volunteers

Summary BAY m1099 (a 1-deoxynojirimycin derivative) is a glucose analogue which is an -glucosidase inhibitor. Its effects on post-prandial blood glucose and insulin levels was compared with a placebo in 12 healthy male volunteers (6 Blacks and 6 Whites). It produced a similar, significant depression of post-prandial blood glucose and insulin leveles when the groups were assessed separately and when the data were pooled. Although blood insulin levels in Whites were higher than in Blacks, as previously reported, the difference was not statistically significant and did not appear to influence the response to the drug. BAY 1099 produced no objective or subjective untoward effects and appears to warrant further investigation as an adjuvant to dietary control of diabetes mellitus.     

Effects of sensory deafferentation on glucose metabolism of muscles during locomotion

We measured the uptake of a radiolabeled analogue of glucose ([3H]FDG) into muscles during treadmill walking so as to determine whether sensory deafferentation of a limb affects the muscles' metabolic response to the exercise. The muscles on the deafferented side took up less tracer than those in the intact side with exercise, but not at rest. Extensor muscles were more affected than flexors by deafferentation. This agrees with the proposal that "reflex" inputs adjust the level of recruitment of motor units by central pattern generators.     

Reversibility of the acute toxic effect of Cyclosporin A on pancreatic B cells of Wistar rats

Summary. This study investigated if and to what extent the acute toxic effect of Cyclosporin A on pancreatic Wistar rat B cells is reversible. After 2 weeks of treatment rats developed marked glucose intolerance accompanied by reduced pancreatic insulin content due to a loss of B cells, diminished islet DNA synthesis and decreased B-cell insulin content. Cyclosporin A had accumulated in the pancreas. Three weeks after withdrawal of Cyclosporin A, pancreatic tissue concentrations of Cyclosporin A were still 100 times larger than in serum. Glucose tolerance, however, had already improved, associated with an increase of B-cell insulin content and apparent islet replication, and the insulin response of isolated islets was reduced. Five weeks after the withdrawal of Cyclosporin A, glucose tolerance was normal, but pancreatic insulin content and relative B-cell volume were still diminished in comparison to vehicle-treated controls. Eight weeks after withdrawal, the morphometric parameters had also been normalized. The results suggest that the loss of pancreatic B cells is caused by a toxic destruction, possibly combined with an apparent decrease of replicatory activity. The acute toxic effects of Cyclosporin A in pancreatic B cells are stepwise reversible.     

Body weight set point studies in weanling rats with dorsomedial hypothalamic lesions (DMNL rats)

In order to further characterize a previously postulated "organismic" set point, weanling DMNL and control (CON) rats were maintained on lab chow ad lib (AL) for 55 post-operative days. Subsequently, some DMNL and CON rats were food-restricted (REST) to 80% of the food intake of their AL-fed counterparts for 24 days. At this point, representative rats from each group were killed by decapitation and the remaining animals were re-fed AL and killed 7 and 22 days thereafter. At the end of REST, both DMNL and CON showed significant weight loss, which was greater in CON than in DMNL rats. After 7 days of refeeding, DMNL rats normalized their body weights but re-fed CON still weighed less than AL-fed CON 22 days after refeeding. Food intake in formerly REST groups overshot on refeeding for 7 days, but this was significant only in DMNL rats. Notably, during this time formerly REST-DMNL ate as much as AL-fed CON. Efficiency of food utilization was normal in DMNL during AL feeding and became reduced on REST as it did in REST-CON. Notably, on refeeding formerly REST-DMNL rats overshot that of AL-fed DMNL rats by the same magnitude as previously REST-CON overshot the values of AL-fed CON. After 22 days of refeeding, this overshoot was still evident in DMNL but not in CON. At the end of the REST period, plasma insulin and glucose were similar in AL-fed DMNL and AL-fed CON. They were significantly and comparably reduced in both REST-DMNL and REST-CON compared to the AL-fed DMNL and AL-fed CON. On refeeding these changes normalized within seven days. At the end of REST, plasma free fatty acid concentrations were higher in REST-DMNL and REST-CON than in AL-fed DMNL and AL-fed CON. After seven days of refeeding they normalized only in formerly REST-CON. Plasma glycerol and total protein were normal throughout all groups, as was carcass protein. Carcass fat was equivalently reduced in both DMNL and CON at the end of REST and normalized 7 days after refeeding. AL-DMNL had the same carcass fat as AL-CON and REST-DMNL had the same carcass fat as REST-CON. In conjunction with previously reported normal anabolic hormone levels the data suggest that DMNL rats are not growth-retarded but are merely scaled down in size without compromise of their homeostatic competence. We take this as strong evidence for the existence of an "organismic" set point.     

Chronic Intake of Energy Drinks and Their Sugar Free Substitution Similarly Promotes Metabolic Syndrome

Energy drinks containing significant quantities of caffeine, taurine and sugar are increasingly consumed, particularly by adolescents and young adults. The putative effects of chronic ingestion of either standard energy drink, Mother^TM (ED), or its sugar-free formulation (sfED) on metabolic syndrome were determined in wild-type C57BL/6J mice, in comparison to a soft drink, Coca-Cola (SD), a Western-styled diet enriched in saturated fatty acids (SFA), and a combination of SFA + ED. Following 13 weeks of intervention, mice treated with ED were hyperglycaemic and hypertriglyceridaemic, indicating higher triglyceride glucose index, which was similar to the mice maintained on SD. Surprisingly, the mice maintained on sfED also showed signs of insulin resistance with hyperglycaemia, hypertriglyceridaemia, and greater triglyceride glucose index, comparable to the ED group mice. In addition, the ED mice had greater adiposity primarily due to the increase in white adipose tissue, although the body weight was comparable to the control mice receiving only water. The mice maintained on SFA diet exhibited significantly greater weight gain, body fat, cholesterol and insulin, whilst blood glucose and triglyceride concentrations remained comparable to the control mice. Collectively, these data suggest that the consumption of both standard and sugar-free forms of energy drinks induces metabolic syndrome, particularly insulin resistance.     

The Effects of Gold Kiwifruit Intake Timing with or without Pericarp on Postprandial Blood Glucose Level

The purpose of this study was to examine how gold kiwifruit pericarp (pericarp is defined as the skin of the fruit) consumption and the timing thereof affect the postprandial blood glucose profile. The study was conducted on twelve healthy volunteers (six men and six women). According to our results, the simultaneous intake of gold kiwifruit with bread and the prior intake of gold kiwifruit evidently suppressed the postprandial blood glucose elevation compared with exclusive bread intake. There was no significant difference in postprandial blood glucose changes between the ingestion of gold kiwifruit pericarp and pulp and that of gold kiwifruit pulp only. The highest postprandial blood glucose elevation was suppressed by 27.6% and the area under the blood glucose elevation curve by 29.3%, even with the exclusive ingestion of gold kiwifruit pulp. We predicted that the ingestion of both the pericarp and pulp of gold kiwifruit would reduce the postprandial blood glucose elevation to a greater extent than that of gold kiwifruit pulp only; however, there was no significant difference between the two. These results indicate that gold kiwifruit consumption significantly suppresses the postprandial blood glucose elevation regardless of pericarp presence or absence and the timing of ingestion.     

Foxtail Millet Improves Blood Glucose Metabolism in Diabetic Rats through PI3K/AKT and NF-κB Signaling Pathways Mediated by Gut Microbiota

Foxtail millet (FM) is receiving ongoing increased attention due to its beneficial health effects, including the hypoglycemic effect. However, the underlying mechanisms of the hypoglycemic effect have been underexplored. In the present study, the hypoglycemic effect of FM supplementation was confirmed again in high-fat diet and streptozotocin-induced diabetic rats with significantly decreased fasting glucose (FG), glycated serum protein, and areas under the glucose tolerance test (p < 0.05). We employed 16S rRNA and liver RNA sequencing technologies to identify the target gut microbes and signaling pathways involved in the hypoglycemic effect of FM supplementation. The results showed that FM supplementation significantly increased the relative abundance of Lactobacillus and Ruminococcus_2, which were significantly negatively correlated with FG and 2-h glucose. FM supplementation significantly reversed the trends of gene expression in diabetic rats. Specifically, FM supplementation inhibited gluconeogenesis, stimulated glycolysis, and restored fatty acid synthesis through activation of the PI3K/AKT signaling pathway. FM also reduced inflammation through inhibition of the NF-κB signaling pathway. Spearman’s correlation analysis indicated a complicated set of interdependencies among the gut microbiota, signaling pathways, and metabolic parameters. Collectively, the above results suggest that the hypoglycemic effect of FM was at least partially mediated by the increased relative abundance of Lactobacillus, activation of the PI3K/AKT signaling pathway, and inhibition of the NF-κB signaling pathway.     

Acute Low-Intensity Treadmill Running Upregulates the Expression of Intestinal Glucose Transporters via GLP-2 in Mice

The effects of exercise on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training increases the expression of molecules involved in carbohydrate digestion and absorption. Exercise was also shown to increase the blood concentration of glucagon-like peptide-2 (GLP-2), which regulates carbohydrate digestion and absorption in the small intestine. Therefore, we investigated the effects of exercise on the expression of molecules involved in intestinal digestion and absorption, including GLP-2. Six-week-old male mice were divided into a sedentary (SED) and low-intensity exercise (LEx) group. LEx mice were required to run on a treadmill (12.5 m/min, 1 h), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest, and plasma, jejunum, ileum, and colon samples were collected, followed by analysis via IHC, EIA, and immunoblotting. The levels of plasma GLP-2 and the jejunum expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter 2 (GLUT2) were higher in LEx mice. Thus, we showed that acute low-intensity exercise affects the expression of molecules involved in intestinal carbohydrate digestion and absorption via GLP-2. Our results suggest that exercise might be beneficial for small intestine function in individuals with intestinal frailty.