Abnormal carbohydrate metabolism is a commonly encountered feature of malaria in people, and similar derangements have been detected in veterinary patients with canine babesiosis. Glucose, the major metabolic fuel source, is a key resource in critically ill patients as they mount an immunological response to infection and inflammation. The ability of the individual to effectively mobilise, distribute and utilise glucose is a major determinant of morbidity and mortality. Hypoglycaemia has been identified as a life threatening metabolic complication in almost 20% of severely ill dogs suffering from babesiosis due to Babesia rossi infection. Insulin and glucagon are the primary hormones involved in glucose homeostasis. Insulin lowers blood glucose concentration by facilitating cellular uptake and utilisation of glucose. Hyperinsulinaemia as a result of inappropriate insulin secretion may precipitate hypoglycaemia, and has been identif ed as a cause of hypoglycaemia in human and murine malaria. A similar phenomenon may exist in canine babesiosis. This prospective, cross-sectional, observational study, including 94 dogs with naturally acquired virulent babesiosis, sought to investigate and characterise the relationship between blood glucose concentrations and insulin concentrations in cases of canine babesiosis. Pre-treatment jugular blood samples were collected for simultaneous determination of plasma glucose and insulin concentrations. Animals were retrospectively divided into three groups: hypoglycaemic (plasma glucose concentration < 3.3 mmol/L; n=16), normoglycaemic (3.3-5.5 mmol/L; n=62), and hyperglycaemic (> 5.5 mmol/L; n=16). The median plasma insulin concentrations (IQR in parentheses) for the hypoglycaemic, normoglycaemic and hyperglycaemic groups were 10.7 pmol/L (10.7-18.8 pmol/L), 10.7 pmol/L (10.7-29.53 pmol/L; i.e below the detection limit of the assay), and 21.7 pmol/L (10.7-45.74 pmol/L), respectively. Statistical analysis revealed no significant difference in insulin concentration between the three groups. These results suggest that insulin secretion was appropriately suppressed in these dogs. Only two dogs had elevated insulin concentrations, one of which was hypoglycaemic. The median time since last meal (available for 87 dogs) was 24 hours (IQR 2-4 days), constituting a significant period of illness-induced starvation. We conclude that hyperinsulinaemia is not a cause of hypoglycaemia in virulent canine babesiosis. It is speculated that prolonged fasting due to disease-induced anorexia, in addition to increased glucose consumption, depletion of hepatic glycogen stores, and hepatic dysfunction with impaired gluconeogenesis, may play important roles in the pathophysiology of hypoglycaemia in canine babesiosis. / Dissertation (MMedVet)--University of Pretoria, 2010. / Companion Animal Clinical Studies / unrestricted

In the past few years, 8 additional members of the facilitative hexose transporter family have been identified, giving a total of 14 members of the SLC2A family of membrane-bound hexose transporters. To determine which of the new hexose transporters were expressed in muscle, mRNA concentrations of 11 glucose transporters (GLUTs) were quantified and compared. RNA from muscle from 10 normal volunteers was subjected to RT-PCR. Primers were designed that amplified 78- to 241-base fragments, and cDNA standards were cloned for GLUT1, GLUT2, GLUT3, GLUT4, GLUT5, GLUT6, GLUT8, GLUT9, GLUT10, GLUT11, GLUT12, and GAPDH. Seven of these eleven hexose transporters were detectable in normal human muscle. The rank order was GLUT4, GLUT5, GLUT12, GLUT8, GLUT11, GLUT3, and GLUT1, with corresponding concentrations of 404 ± 49, 131 ± 14, 33 ± 4, 5.5 ± 0.5, 4.1 ± 0.4, 1.2 ± .0.1, and 0.9 ± 0.2 copies/ng RNA (means ± SE), respectively, for the 10 subjects. Concentrations of mRNA for GLUT4, GLUT5, and GLUT12 were much higher than those for the remainder of the GLUTs and together accounted for 98% of the total GLUT isoform mRNA. Immunoblots of muscle homogenates verified that the respective proteins for GLUT4, GLUT5, and GLUT12 were present in normal human muscle. Immunofluorescent studies demonstrated that GLUT4 and GLUT12 were predominantly expressed in type I oxidative fibers; however, GLUT5 was expressed predominantly in type II (white) fibers.

Aujourd’hui, face à l’épidémie d’obésité, de plus en plus de personnes ont recours à la chirurgie bariatrique, qui permet une perte de poids importante et une amélioration des conditions métaboliques associées à l’obésité. L’adaptation gastro-intestinale après la chirurgie et ses conséquences métaboliques sont cependant peu connues. Nous avons développé des modèles murins de bypass gastriques et de gastrectomie longitudinale (sleeve) et nous avons caractérisé l’adaptation morphologique et fonctionnelle de l’épithélium gastro-intestinal après ces chirurgies afin de comprendre l’origine des améliorations métaboliques. Nous avons montré que l’estomac était remodelé après les deux chirurgies, suggérant une augmentation de la production acide par les cellules pariétales et une altération de la production de gastrine et de ghréline. Après le bypass, l’anse alimentaire était hyperplasique et la consommation intestinale de glucose était augmentée chez le rat et l’homme; après la sleeve, l’absorption de glucose lors du repas était diminuée. De plus, l’augmentation du nombre de cellules entéroendocrines observée après le bypass, et l’augmentation de leur densité après la sleeve pourraient participer à l’hypersécrétion des hormones incrétines. L’ensemble de ces mécanismes pourrait contribuer à améliorer le contrôle de la glycémie. Enfin, le mini-bypass chez le rat a induit une malabsorption protéique et des fuites énergétiques majeures qui n’étaient pas compensées par l’hyperplasie intestinale ou l’augmentation de l’expression des transporteurs de peptides. Cette thèse montre l’importance du tractus gastro-intestinal dans les conséquences métaboliques de la chirurgie bariatrique / In today’s global epidemic of obesity, more and more people are undergoing bariatric surgery, which is the best known treatment available to lose weight and treat obesity-associated diseases. Yet, little is known about gastrointestinal (GI) adaptation and its metabolic consequences after surgery. We developed original models of Roux-en-Y gastric bypass (RYGB), mini-bypass (MGB) and vertical sleeve gastrectomy (VSG) in rats, and we characterized the morphological and functional adaptations of the GI epithelium after these surgeries in order to understand the origin of the observed metabolic improvements. We reported profound changes in the remaining gastric mucosa of rats having undergone RYGB and VSG, suggesting an increase in acid production by parietal cells and an impaired production of gastrin and ghrelin. In RYGB rats and patients, the alimentary limb was hyperplasic and intestinal glucose consumption was increased. After VSG, the absorption of glucose during meals appeared diminished. These adaptations could participate in the lowering of blood glucose after surgery. In addition, the increased number of enteroendocrine cells observed in RYGB rats and patients, and their increased density in VSG rats, could contribute to the higher secretion of incretin hormone and improved glycemic control in operated individuals. Finally, we demonstrated in rats that the MGB was more malabsorptive than the RYGB. Indeed, we observed an increased fecal loss of nitrogen and energy despite intestinal overgrowth and higher expression of peptide transporters. This thesis brings new insight to the role of the GI tract in the metabolic outcomes of bariatric surgeries

Diabetes mellitus is a potentially lethal disease that affects 7.6 percent of American people. In the US, it is recognized as the 6th leading cause of death. Failure to control blood glucose levels (BGL) in patients with either type of diabetes can lead to other serious complications as well, such as loss of limb, blindness and other health problems. Controlling and monitoring the BGL in post-op and intensive care patients in the hospital is also vital to their health. Currently the most reliable method of monitoring BGL is through an invasive procedure which monitors the amount of glucose in blood directly. A non-invasive glucose sensor would drastically improve the treatment of sensitive patients, and serve to improve the quality of diabetic patients' lives. This glucose sensor is strongly based upon the mercury sensor developed by F.E. Hernandez and his colleagues. Glucose is used as a reducing agent to reduce mercury from Hg2+ to Hg0, which will form amalgams with the gold nanorods in solution. The change in aspect ratio of gold nanorods leads to a change in the UV-Visible spectrum of the solution. The blue shift seen was measured and correlated with the glucose concentration of the system. The system was then tested varying conditions such as pH, temperature, gold nanorod concentration, and mercury concentration. A preliminary study of the kinetics of the reaction was also done. The results showed a limit of detection of 1.58x10-13 and a linear dynamic range covering the concentrations of human tear glucose levels that are currently cited in the literature.

No description available.

Introduction: Brief vigorous exercise can enhance glycemic control. Limited work has investigated the effect of simple, practical interventions that require no specialized equipment. We examined the effect of bodyweight exercise (BWE) on acute glycemic control using continuous glucose monitoring (Abbott Libre Sense) under controlled dietary conditions This study was registered as a clinical trial (NCT05144490). Methods: Twenty-seven healthy adults (8 males, 19 females; age: 23±3 y) completed two virtually supervised trials in random order ~1 wk apart. The trials involved an 11-min BWE protocol that consisted of five, 1-min bouts performed at a self-selected pace interspersed with 1-min active recovery periods or a non-exercise sitting control period (CON). Food intake was standardized for each participant using pre-packaged meals supplied over 24 h. Results: Mean rating of perceived exertion for BWE was 14±2 (6-20 scale). Mean HR over the 11-minute the BWE protocol was 147±14 bpm which corresponded to 75% of age-predicted maximal HR. Mean 24-h glucose after BWE and CON was not different (5.0±0.4 vs 5.0±0.5 mM respectively; p=0.39). Postprandial glucose responses were also not different between trials after ingestion of a 75 g glucose drink, lunch, dinner and breakfast meals after each intervention. Measures of glycemic variability were not different between conditions. Conclusion: A single session of BWE did not alter acute glycemic control in healthy, young adults. This study demonstrates the feasibility of conducting a remotely supervised BWE intervention using CGM under free-living conditions. Future studies should investigate the effect of repeated sessions of BWE training as well as responses in people with impaired glycemic control. / Thesis / Master of Science (MSc) / We investigated the effect of brief bodyweight exercise (BWE) on glycemic control. This refers to the ability to maintain blood sugar within a healthy range. Glycemic control was assessed with a small device called a continuous glucose monitor (CGM) that is inserted just below the skin. Healthy adults completed a virtually supervised 11-minute BWE protocol or an equivalent period of sitting. There was no difference in glycemic control measured over 24 hours following the BWE compared to sitting under standardized dietary conditions. Future studies should investigate the effect of repeated sessions of BWE training as well as responses in people with impaired glycemic control.

Diabetes mellitus is a major public health concern. Although the accessible novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance (IR) and loss of &beta;-cell mass and function. Therefore, the search for naturally occurring, low-cost, and safe compounds that could enhance insulin sensitivity and protect functional &beta;-cell mass can be an effective strategy to prevent this disease. Kaempferol, a flavonol present in various medicinal herbs and edible plants, has been shown to elicit various pharmacological activities in preclinical studies. However, studies investigating the effect of kaempferol on diabetes are limited. In this dissertation, I explored the anti-diabetic potential of dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. First, kaempferol was supplemented in the diet to determine whether it can prevent IR and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. To evaluate its efficacy for treating diabetes, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice. The results demonstrated that long-term oral administration of kaempferol prevents HFD-induced metabolic disorders in middle-aged obese mice. Oral administration of kaempferol improved glucose intolerance and insulin sensitivity, and this effect was associated with increased Glut4 and AMPKa expression in muscle and adipose tissues. Consistent with our findings from the in iii vitro study in C2C12 muscle cell line, these findings suggest that kaempferol may reduce IR at the molecular level by improving glucose metabolism in peripheral tissues. In the second study, dietary kaempferol supplementation prevented hyperglycemia and glucose intolerance by protecting &beta;-cell against the induced damage in obese STZ-induced diabetic mice. In the third study, the administration of kaempferol by oral gavage significantly ameliorated hyperglycemia and glucose intolerance and reduced the incidence of diabetes from 100 % to 77.8% in lean STZinduced diabetic mice. This kaempferol effect was associated with reduced hepatic glucose production, the primary contributor to hyperglycemia, and increased glucose oxidation in the muscle of diabetic mice. Kaempferol treatment restored hexokinase activity in the liver and skeletal muscle and reduced pyruvate carboxylase (PC) activity and glycogenolysis in the liver. Unlike its effect on T2D mice, kaempferol effect in lean STZ-induced diabetic mice was not associated with changes in plasma insulin levels. In the last study, we found that administration of kaempferol by oral gavage significantly improved blood glucose control by suppressing hepatic glucose production and improving glucose intolerance in obese insulin-resistant mice. Similar to its effect in old obese mice, kaempferol enhanced whole-body insulin sensitivity. Kaempferol increased Akt and hexokinase activity and decreased PC activity in the liver. However, kaempferol did not exert any changes in glucose metabolism or insulin sensitivity when administered to healthy lean mice. Overall, findings from these studies provide new insight into the role of kaempferol in the regulation of glucose homeostasis and suggest that kaempferol may be a naturally occurring anti-diabetic compound by improving insulin sensitivity, improving glucose regulation and metabolism, and preserving functional &beta;-cell mass. / Ph. D.

This study was designed to evaluate the effect of glucose on plasma pyridoxal 5'- phosphate (PLP) concentration. The objective was to determine whether there was a negative relationship between glucose ingestion and plasma PLP concentration and to evaluate the possible mechanism of decreased PLP after acute glucose ingestion. Seven healthy subjects (three males and four females) completed the oral glucose tolerance test (OGTT) on three separate occasions over a period of three weeks. Each week, subjects ingested the assigned solutions (a water solution with artificial sweetener equivalent to 25g glucose, a 25g glucose or a 75g glucose load) in a randomized order. Plasma PLP, pyridoxal (PL), 4-pyridoxic acid (4-PA), pyridoxine (PN), glucose, insulin, alkaline phosphatase (AP) activity and red blood cell PLP concentrations were measured at 0 (fasting) (TO), 1 (T1), 2 (T2) and 3 (T3) hours. The mean vitamin B-6 intake based on two 3-day dietary records was 1.57 ± 0.34 mg/day. All subjects had normal glucose tolerance. There were gender differences among the three solutions. Both the water solution and the 75g glucose load showed a significant decrease in the mean plasma PLP concentration was observed at T3 for males and at T2 for females (p<0.05). An overall mean decrease of 20% (9nmol/L) and 15% (7 nmol/L) was observed for males and females, respectively, after the 75g glucose load. The 25g glucose load resulted in a lower decrease in the mean plasma PLP concentration at each time point compared with the 75g glucose load, but no significant difference was found in the level of decrease between the two glucose loads. Both genders had a non-significant increase in the mean plasma PL and PN concentrations for the three solutions. Mean plasma 4-PA concentration was decreased at T1 with the three solutions. There was no significant change in the plasma AP activity at any time points after the three solutions. In addition, no significant increase in mean red blood cell PLP concentration was observed at all time points after the three solutions. This study found a negative relationship between glucose ingestion and plasma PLP concentration. However, it did not provide clear evidence for the hypothesized mechanism of the decreased plasma PLP concentration after acute glucose load. Further studies are required to determine the mechanism by which glucose decreases plasma PLP concentration. / Graduation date: 2000

The purpose of this study was to determine the relationship between the overall changes in concentration of plasma pyridoxal 5'-phosphate (PLP), red blood cell PLP (rbc PLP) and plasma glucose during an oral glucose tolerance test (OGTT) in persons with diabetes mellitus (DM), and to test the hypothesis that the decrease in plasma PLP concentration that occurs with increasing plasma glucose would be explained by a subsequent increase in rbc PLP concentration. A second objective was to compare the distribution of PLP between the red blood cell and the plasma (as measured by the rbc PLP/ plasma PLP ratio) in persons with diabetes to the distribution in non-diabetic controls. The third objective was to measure fasting plasma alkaline phosphatase (AP) activity, and to compare it to fasting plasma PLP concentrations, fasting rbc PLP concentrations, and the rbc PLP/plasma PLP ratio. The purpose of this third objective was to test the hypothesis that an increased plasma AP activity in persons with DM would be associated with decreased plasma PLP and increased rbc PLP concentrations. The study included 8 persons (3F; 5M) with insulin dependent diabetes mellitus (IDDM), 9 persons (5F; 4M) with non-insulin dependent diabetes mellitus (NIDDM) and 18 healthy control individuals (9F; 9M). All subjects were given a 75 gm oral D-glucose dose, and blood was drawn at 0 (fasting), 30, 60 and 120 minutes after the glucose load. Plasma glucose, PLP, insulin, and rbc PLP concentrations were measured at all time points during the OGTT. Fasting plasma alkaline phosphatase (AP) activity, percent glycosylated hemoglobin (%GlyHb), and the ratio between fasting rbc PLP and fasting plasma PLP were also determined. In general, females with DM were in poorer diabetic control as compared to males with DM. Mean fasting glucose levels, %GlyHb and body mass index (BMI) were highest in females with DM as compared to all other groups, and fasting insulin was nearly 2x higher in females with NIDDM as compared to males with NIDDM. There was an overall decrease in plasma PLP during the OGTT with increasing plasma glucose, which agrees with results from other studies. The overall decrease in plasma PLP (as measured by the negative, cumulative area under the curve: -AUC plp) was significantly correlated with the overall increase in plasma glucose (as measured by the positive, cumulative area under the curve: +AUC glu) for all study groups. The relationship was stronger in all males, and control females as compared to females with diabetes (p< 0.001 vs. p< 0.01, respectively). This difference was in part explained by lower mean fasting PLP levels in females with DM (19.3 nmol/L), as compared to males with DM (47.2nmol/L) and male and female controls (35.4 nmol/L and 34.0 nmol/L, respectively). The changes in rbc PLP during the OGTT were minimal, and did not significantly correlate with the increase in plasma glucose or the decrease in plasma PLP. Thus, the acute drop in plasma PLP concentration that occurred during the OGTT was not explained by a subsequent increase in rbc PLP concentration, as had been hypothesized. However, the higher than normal % glycosylated hemoglobin levels along with elevated rbc PLP concentrations in persons with diabetes as compared to controls suggests that chronically elevated blood glucose can contribute to increased rbc PLP concentrations. This was the first study to date that has measured rbc PLP in persons with diabetes mellitus. Rbc PLP values for persons with DM were 20-40% greater than respective control values at all time points during the OGTT. These differences between mean rbc PLP in persons with DM as compared to control groups were all statistically significant (p< 0.05) with the exception of the difference in the mean fasting rbc PLP value for females with NIDDM as compared to controls. The mean values ± standard deviations (SD) for fasting rbc PLP (nmol/L) were as follows: Females-IDDM, 49.5 ± 6.5; NIDDM, 39.3 ± 4.9; controls, 31.4 ± 9.0; Males-IDDM, 37.8 ± 10.9; NIDDM, 45.6 ± 12.3; controls, 28.3 ± 4.4. The ratio of fasting rbc PLP concentration to fasting plasma PLP concentration was 2-3x higher in females with DM as compared to control females and all male groups. Females with IDDM had a ratio of 3.2, and the ratio for females with NIDDM was 2.2. The ratios for all male groups, and control females were approximately 1:1, with a range of 0.8-1.2. The mean fasting plasma AP activity was within the normal range for all study groups. However, females with DM had higher AP activity (0.543 μkat/L) as compared to female controls and males with DM (0.408 μkat/L, .425 μkat/L, respectively p<0.05). There were no significant differences in mean fasting plasma AP activity between any male group (range 0.390-0.465 μkat/L). These results suggest that increased plasma glucose levels, increased AP activity, and overall poor glycemic control contribute to decreased plasma PLP concentrations, increased rbc PLP concentrations, and possibly to changes in the PLP distribution within the body. / Graduation date: 1994

No description available.