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A high blood glucose concentration is one of many factors that can contribute to the development of type 2 diabetes, which is a world-spreading disease. Many studies have been done on products that can lower the glycaemic response and one of these products is the grain rye. Whole grain rye and endosperm from rye have shown positive results on the blood glucose and insulin responses after carbohydrate intake in former studies. In this randomised crossover meal study, a special rye extract, rich in soluble fibres, was used to investigate if it gave the same blood glucose and insulin results as in previous studies. The rye product that was used is this study was obtained by a confidential extraction process. The rye extract was found to contain 20.4 g dietary fibres per 100 g dry weight and the rye drink that was served to the test subjects contained 4 g dietary fibre. The rye product and the reference product were both mixed with Fun Light soda for better taste. After the rye or reference drinks had been taken, white bread and water was consumed. In this randomised crossover intervention study, 16 healthy subjects participated and they were all recruited from Lund University. The subjects were men and women in the age of 20-33 with normal fasting blood glucose concentrations and a BMI range of 19-26. The subjects were randomly assigned to drink the rye drink or the reference drink on the first intervention day and the other drink the second time. On the intervention days the blood glucose and insulin concentrations were immediately determined by capillary measurement at fasting conditions (time -15) before the subjects began to drink their test- or reference drink during 15 minutes. After the drinks had been taken, the blood sugar concentration was measured (time 0) before the white bread and water were ingested. The blood sugar and insulin concentrations were then measured at 15, 30, 45, 60, 90, 120 and 180 minutes from when the test subjects started to eat the white bread. The rye product displayed a lower incremental glucose response (p= 0.008) and a lower iPeak value (maximum value) than the reference product (p=0.002). Both GP and GPI were higher for the rye meal (p= 0.009 and p= 0.018). The insulin values did not differ significantly from each other in comparison with the reference meal. The rye product showed similar reduced blood glucose responses compared to its reference product as previous studies have shown. In contrast, the rye product did not show the same positive result on the insulin values. The rye products relatively lower blood glucose response may largely be due to the rye products content of arabinoxylan, which explains the rye drinks viscosity. The viscosity has in previous studies resulted in a slower gastric emptying rate and a slower absorption of glucose in the small intestine like it also looks to have done in this study.

Background: Abnormalities in postprandial lipid metabolism may explain, in part, the 2 to 4 fold increased risk of coronary heart disease (CHD) in diabetic individuals compared with the general population. Aims: To develop an Oral Triglyceride Tolerance Test (OTTT) to evaluate reliably post challenge metabolism and to determine whether more physiologic insulin profiles can improve lipid responses in diabetic subjects. Methods: Post 50g fat and 50g carbohydrate challenge triglyceride and glucose profiles were measured 2 hourly for 8 hours on 2 occasions to establish test reproducibility and to characterise responses in type 2 diabetic and non diabetic subjects. The potential effects on post challenge lipid and glucose metabolism of modifying endogenous insulin delivery via the portal system or augmenting post challenge systemic insulin levels were assessed using the OTTT. Results: Reproducible post challenge triglyceride, NEFA, glycerol, glucose, insulin and C peptide responses were obtained in non diabetic and type 2 diabetic subjects. In type 2 diabetic subjects both ultra rapid endogenous and exogenous insulin delivery decreased post challenge hyperglycaemia and improved NEFA-glycerol suppression, relative to placebo and soluble insulin respectively. Enhancing portal insulin secretion had no effect on triglyceride levels. Increasing peripheral insulin levels showed no difference in triglyceride profiles between insulins tested although 6 hour triglyceride excursions were less than endogenous enhancement. Type 1 diabetic subjects displayed triglyceride profiles similar to non diabetic subjects, and reduced triglyceride excursion was seen with soluble than analogue insulin replacement. Conclusion: Increasing the peripheral to portal insulin ratio may relieve hepatic exposure to chronic hyperinsulinaemia characteristic of type 2 diabetes thus reducing post challenge triglyceride excursions. Improving postprandial metabolism, by delaying atherogenesis, may help decrease the risk of CHD.

Mitochondrial dysfunction is considered as a key mechanism of aging but little is known about the impact of mitochondrial biogenesis. Mitochondrial DNA (mtDNA) copy number control is an important aspect of mitochondrial biogenesis and is highly regulated in eukaryotic organisms. By studying mtDNA copy number, our aim is to gain a better understanding of the relationship between mitochondrial biogenesis and aging. We developed an optimized protocol for measuring mtDNA copy number in Caenorhabditis elegans using quantitative real-time PCR (qPCR). We investigated how mtDNA regulation is affected by a variety of aging-related pathways. We found the insulin/IGF-1 signaling (IIS) pathway regulates mtDNA content in a DAF-16- and UCP-4-dependent manner. By utilizing RNA interference (RNAi) against polg-1, we showed that mitochondrial stress likely modulates lifespan through the IIS pathway. Our work identifies IIS as a communications pathway between mitochondria and the nucleus in modulating mitochondrial biogenesis and lifespan in Caenorhabditis elegans.

Thirty-two Quarter horse mares (468 to 668 kg BW; 3 to 19 yr) were utilized in a randomized complete block design. Animals were blocked by expected foaling date and randomly assigned to treatments within block. Treatments began 110 d prior to expected foaling date and were arranged as a 2 x 2 factorial consisting of two planes of nutrition, moderate (Mod; 0.5% BW as fed grain/d) or high (High; 1% BW as fed grain/d) and two levels of L-arginine supplementation, 0.21 g/kg BW/d (Arg) or no supplemental Arg (Con; L-alanine to maintain isonitrogenous diets). Mares were housed by block, allowed ad libitum access to water and coastal bermudagrass (Cynodon dactylon) hay, and fed commercial grain twice daily in individual stalls. A modified frequent sampling i.v. glucose tolerance test (FSIGT) was performed on mares during the 11th month gestation and on foals at 5 and 30 d of age. Jugular catheters were placed 1 h before FSIGT, and horses were allowed ad libitum access to bermudagrass hay and water throughout. After a baseline plasma sample was collected, a glucose bolus of 0.3 g/kg BW was administered. Blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, and 19 min. At minute 20, an insulin bolus of 30 mU/kg BW was administered. Blood samples continued to be collected at 22, 23, 24, 25, 27, 30, 35, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 min. Samples were placed into tubes containing sodium heparin, immediately placed on ice, and centrifuged within 20 min. Plasma was then collected, placed in microtubes and frozen at -20 degrees C for later analysis. Glucose concentrations were analyzed using a colorimetric assay and insulin concentrations determined using a commercial RIA kit. There was no influence of dietary treatment on mare glucose area under the curve (AUCg) or peak glucose (PG) and insulin (PI) concentrations (P >= 0.55). Mare insulin area under the curve (AUCi) tended to be influenced by the interaction between nutritional plane and ARG supplementation (P <= 0.06) with HighCon mares having greater AUCi than ModCon (P <= 0.05), and HighCon mares having greater AUCi than mares fed HighArg (P <= 0.05). Foal AUCg, AUCi, and PI were not influenced by maternal diet. However, PG concentration in foals tended to be influenced by mare AA supplementation with foals from Con mares having higher concentrations compared to Arg (P <= 0.09) An influence of age was observed on foal AUCg and AUCi. Foal AUCg was greater at 5 d compared to 30 d (P <= 0.003). Foal AUCi tended to be greater at 30 d compared to 5 d (P <= 0.08). Data suggest maternal plane of nutrition and arginine supplementation can alter mare and foal glucose and insulin dynamics.

Thesis (PhD) -- University of South Australia, 1992

A five stage selection protocol originally applied to mouse embryonic stem cells (mESCs) was examined for the derivation of insulin producing cells from human embryonic stem cells (hESCs). Insulin gene expression was observed and insulin protein was measured by radioimmunoassay. However, the radioimmunoassay results were shown to be susceptible to false positive findings due to the presence of exogenous insulin within differentiation media and it was concluded that this particular strategy was not ideal for the derivation of insulin producing cells from hESCs. An investigation was then undertaken regarding the in vivo differentiation of cells derived from hESCs seeded within 3D scaffolds to determine if this would result in the derivation of insulin producing cells. Within scaffolds there were abundant cells which stained positively for ectoderm lineage markers including nestin. Cells which stained positively for markers of endothelial progenitors representing the mesoderm lineage were also observed and rare cells stained for endoderm markers including insulin. These investigations also demonstrated that transplanting scaffolds seeded with cells derived from hESCs between the liver lobules of immunodeficient mice could lead to the formation of teratomas. Factors that may have influence the formation of teratomas were further investigated and it was demonstrated that teratoma formation was inhibited by altering in vitro treatment of cells. An in vitro investigation was then performed to determine the extracellular matrix (ECM) producing capacity of hESCs and differentiated cells derived from hESCs because ECM proteins are required for the formation of 3D structures similar to pancreatic islets. The results from this investigation indicated that differentiated cells produced multiple ECM proteins at substantially higher levels than hESCs. The ECM producing differentiated cells could be useful in the development of surrogate islet like tissue by supplying a suitable ECM structure within a 3D scaffold environment to aid the function of ??-cell surrogates. Furthermore, these differentiated cells derived from hESCs were shown to produce an adhesive basement membrane in vitro, which is derived from human sources, and could be utilized in the derivation, propagation and differentiation of hESCs.

iii, 136 leaves : ill. ; 26 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.) from the Dept. of Physical and Inorganic Chemistry, University of Adelaide, 1972

Thesis (PhD) -- University of South Australia, 1992