Studies on the carbohydrate metabolism of sheep. XIII. The interpretation of changes in the levels of metabolic intermediates after intravenous injection of propionate, succinate and malate

1961 ◽  
Vol 12 (5) ◽  
pp. 913 ◽  
Author(s):  
RL Reid ◽  
SC Mills

Blood levels of pyruvic, citric, and �-oxoglutaric acids in sheep are similar to those in man. Citric acid declines markedly on fasting; levels in ewes with pregnancy toxaemia are not significantly different from those in fasted, pregnant ewes. The presence of low citric acid levels in ewes with pregnancy toxaemia in which blood glucose levels are normal or above may further support the suggestion that there is an interference with glucose utilization in pregnancy toxaemia. Intravenous injection of propionate, succinate, and malate into fasted, pregnant ewes always lowered blood ketones, but it is not known to what extent this response is merely a consequence of increased blood glucose following injection. Injected propionate disappeared more rapidly than injected acetate. Propionate injection into fed, non-pregnant ewes is followed by an immediate increase in blood glucose to high levels; the disappearance of excess glucose appears to follow the pattern of a normal glucose tolerance curve. Blood pyruvic acid increases markedly with blood glucose. Succinate and malate injections are followed by small increases in blood glucose and pyruvic acid. The difficulty of interpreting changes in blood glucose in inadequately trained experimental animals is emphasized. Consistent, significant increases in blood oxalaoetic acid did not occur in response to either propionate, succinate, or malate injection. Blood citric and a-oxoglutaric acids increased markedly after succinate and malate, but not after propionate injection. The data are discussed in relation to metabolic pathways in sheep tissues; it is concluded that this type of in vivo experiment is of limited value.

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 458-458
Author(s):  
Andrea Ramos-Lopez ◽  
Luis Mojica ◽  
Armando Gomez-Ojeda ◽  
Maciste Macias-Cervantes ◽  
Claudia Luevano-Contreras

Abstract Objectives In silico, biochemical, in vitro, and in vivo assays have shown that black bean hydrolyzed protein (HPF) could decrease glucose absorption by inhibiting digestive enzymes and blocking gastrointestinal transporters. Therefore, the objective was to evaluate the acute effect of different doses of HPF on glucose levels in adults with normal glucose tolerance (NGT) and with prediabetes. Methods A double-blind, placebo-controlled, randomized clinical trial was conducted on 31 adults with NGT and 24 adults with prediabetes. Participants were 25–50-year-old and with a body mass index (BMI) between 25–34.9 kg/m2. After consent, participants were randomized into four groups, placebo or the corresponding HPF (powder) treatment (D1:2.5 g, D2:3.7 g, D3:5 g). Subjects received the placebo, 120 mL of a commercial beverage (Be-light), or the corresponding HPF dose dissolved in 120 mL of Be-light. An oral glucose tolerance test (OGTT) (75 g glucose) was used to measure glucose tolerance before treatment (initial). A second OGTT was used to evaluate the acute effect of the HPF, and blood samples were collected at 0, 60, 120, and 150 min, and blood glucose levels were measured. Data were analyzed using a one-way ANOVA and paired Student's t-test. Results Participants with NGT: the D3 group showed a decrease in blood glucose area under the curve (AUC) when compared with the D1 group (13,639.2 ± 1585.9 vs. 16,756.6 ± 2709 mg · min/dL; P = 0.05). However, there was no difference with the placebo group (14,073.7 ± 1825.9 mg · min/dL, P = 0.9). When comparing the initial AUC vs. treatment AUC, the placebo, D2, and D3 groups decreased significantly (P = 0.01). Participants with prediabetes: the D3 group also show a significantly decreased in AUC when compared with the D2 group (19,815 ± 3153 vs. 27,545 ± 5398 mg · min/dL; P = 0.01). However, there was no difference with the placebo group (21,743.5 ± 4503 mg · min/dL, P = 0.8). Additionally, when comparing initial AUC vs. treatment AUC, only the D3 group decreased significantly (P = 0.01). Conclusions The comparison of the acute effect of three different doses of HPF showed a decrease in blood glucose (AUC) in a dose-dependent manner in participants with prediabetes. Funding Sources CONACYT Problemas Nacionales 2016-2081.


2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.


1960 ◽  
Vol 11 (3) ◽  
pp. 346 ◽  
Author(s):  
RL Reid

Data on blood glucose, ketone, and acetic acid values have been obtained over a period of several years from field cases of pregnancy toxaemia and from cases induced experimentally and their controls. When feed intake is controlled, differences between blood glucose and ketone levels in ewes moderately undernourished in late pregnancy are largely dependent on the number of foetuses. The consistency of these differences often allows accurate diagnosis of multiple and single pregnancies. Differences in blood glucose between undernourished monotocous and polytocous ewes disappear when undernutrition becomes severe or in the early stages of fasting after a period of moderate undernutrition. Differences in blood ketones tend to be maintained even after several days of fasting. The level of blood ketones during fasting depends on the previous level of nutrition of the ewe; blood glucose is unaffected by previous level of nutrition. The frequent presence of persistent normoglycaemia in ewes with pregnancy toxaemia is discussed in the light of data presented; it is concluded that the onset of pregnancy toxaemia often occurs in the presence of normal blood glucose levels. Blood volatile fatty acid (V.F.A.) levels are often high in those cases of pregnancy toxaemia which occur largely as a result of severe under nutrition in late pregnancy, in spite of an almost empty rumen. Only acetic acid was detected in six blood samples examined; this is considered to be of metabolic origin, but there is no consistent relationship with blood ketone level. The usual clinical syndrome of pregnancy toxaemia can be classified as acute or subacute. In the latter, cerebral depression reaches a certain stage of severity which is then maintained, survival is often prolonged, and ewes do not become comatose before death. Cases of pregnancy toxaemia induced by under nutrition alone usually show the acute syndrome. Blood ketones are higher in such cases than in fasted ewes showing no clinical signs; the critical blood ketone level appears to be about 30 mg per 100 ml. Cases induced in previously well-nourished ewes by fasting in association with a severe environmental stress are usually subacute; blood ketones are no higher than in ewes not showing clinical signs and are often considerably below 30 mg per 100 ml. The significance of these observations is discussed.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.


2009 ◽  
Vol 296 (3) ◽  
pp. E473-E479 ◽  
Author(s):  
Yukihiro Fujita ◽  
Rhonda D. Wideman ◽  
Madeleine Speck ◽  
Ali Asadi ◽  
David S. King ◽  
...  

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released during meals from endocrine cells located in the gut mucosa and stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar sensing and its downstream events coupled to the release of the incretin hormones are not clearly elucidated. Recently, it was reported that sucralose, a sweetener that activates the sweet receptors of taste buds, triggers incretin release from a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity of α-gustducin, a key G-coupled protein involved in taste sensing, is sometimes colocalized with GIP in rat duodenum. We investigated whether secretion of incretins in response to carbohydrates is mediated via taste receptors by feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d-tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce the blood glucose excursion to a subsequent intraperitoneal glucose tolerance test. Neither oral sucralose nor oral stevia reduced blood glucose levels in Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP levels ∼4-fold and GLP-1 levels ∼2.5-fold postadministration, none of the sweeteners tested significantly increased levels of these incretins. Collectively, our findings do not support the concept that release of incretins from enteroendocrine cells is triggered by carbohydrates via a pathway identical to the sensation of “sweet taste” in the tongue.


2017 ◽  
Vol 32 (3) ◽  
pp. 362-372 ◽  
Author(s):  
Liping Liu ◽  
Jing Tan ◽  
Baoyuan Li ◽  
Qian xie ◽  
Junwen Sun ◽  
...  

Objective To improve the biocompatibility between polylactic- co-glycolic acid membrane and pancreatic stem cells, rat fibroblasts were used to modify the polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet tissue by compound culturing the pancreatic stem cells and the fibroblast-modified polylactic- co-glycolic acid membrane and explored the function of artificial islets in diabetic nude mice. Methods Pancreatic stem cells were cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in dulbecco's modified eagle medium containing activin-A, β-catenin, and exendin-4. The differentiated pancreatic stem cells combined with modified polylactic- co-glycolic acid membrane were implanted subcutaneously in diabetic nude mice. The function of artificial islet tissue was explored by detecting blood levels of glucose and insulin in diabetic nude mice. Moreover, the proliferation and differentiation of pancreatic stem cells on modified polylactic- co-glycolic acid membrane as well as the changes on the tissue structure of artificial islets were investigated by immunofluorescence and haematoxylin and eosin staining. Results The pancreatic stem cells differentiated into islet-like cells and secreted insulin when cultured on fibroblast-modified polylactic- co-glycolic acid membrane. Furthermore, when the artificial islet tissues were implanted into diabetic nude mice, the pancreatic stem cells combined with polylactic- co-glycolic acid membrane modified by fibroblasts proliferated, differentiated, and secreted insulin to reduce blood glucose levels in diabetic nude mice. Conclusion Pancreatic stem cells can be induced to differentiate into islet-like cells in vitro. In vivo, the artificial islet tissue can effectively regulate the blood glucose level in nude mice within a short period. However, as time increased, the structure of the artificial islets was destroyed due to the erosion of blood cells that resulted in the gradual loss of artificial islet function.


2004 ◽  
Vol 107 (2) ◽  
pp. 191-196 ◽  
Author(s):  
Aris SIAFARIKAS ◽  
Katie WATTS ◽  
Petra BEYE ◽  
Timothy W. JONES ◽  
Elizabeth A. DAVIS ◽  
...  

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0±1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA1c (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4±1.7 mmol/l) and 120 (5.0±1.1 mmol/l) min increased significantly relative to baseline (4.1±0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1±21.3 m-units/l) and 120 (34.9±23.6 m-units/l) min compared with baseline (4.7±4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.


2019 ◽  
Vol 35 (4) ◽  
pp. 1398-1406
Author(s):  
Sheryl Joyce B. Grijaldo ◽  
Noel S. Quiming ◽  
Marilou G. Nicolas ◽  
Michael Russelle S. Alvarez

Diabetes mellitus, a complex chronic disease that is associated with hyperglycemia (high blood sugar) affects millions of people worldwide. This study evaluated the hypoglycemic activities of male and female Antidesma bunius, commonly known as currant tree or bignay, extracts in alloxan-treated ICR mice. In addition, the effects of the treatments on blood urea nitrogen (BUN) and creatinine levels were determined. Phytochemical screening using standard protocol was performed. Plant extracts (500 mg/kg) were administered orally via gavage for 14 days and fasting blood glucose (FBG) levels were monitored prior to alloxan-induction on the day of alloxan-induction, and on the 3rd, 7th and 14th days of treatment. Sera were collected on the 14th day to measure the BUN and creatinine levels. Phytochemical screening was performed using standard TLC spray tests. All extracts were found to significantly lower FBG levels compared to the positive (glibenclamide 10 mg/kg) and negative (distilled water) controls (One-way ANOVA, p-value<0.0001). The most active extract, aqueous male A. bunius extract, significantly lowered FBG levels by as much as 61.26±17.89% after the 14th day (paired t-test, p-value = 0.0211). Both BUN and creatinine values were found to be significantly different in the treated mice compared to the controls (One-way ANOVA, p-value = 0.0005 and 0.000479, respectively). The BUN level of all mice was still within normal range, unlike with the creatinine level where only the female and male aqueous A. bunius and female ethanolic A. bunius extracts were within normal range. Phytochemical screening showed the presence of saponins, tannins, and polyphenols, phlobatannins, steroids and terpenoids. This study demonstrates the potential of male and female A. bunius leaf extracts to reduce fasting blood glucose levels. Additional work, pertaining to the identification of possible bioactive compounds and establishing the mechanisms thereof, could be performed.


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