No description available.

No description available.

No description available.

The literature comparing macronutrient metabolism in healthy and diabetic subjects is abundant; however, little data exists on how non-diabetic subjects with insulin resistance handle macronutrient. We did two studies to investigate the postprandial responses to macronutrient in healthy, hyperinsulinemic and type 2 diabetic (T2DM) subjects. In the first study, twenty-five healthy, non-diabetic subjects [9 with fasting serum insulin (FSI) <40pmol/L; 8 with 40 ≤ FSI < 70pmol/L; and 8 with FSI ≥ 70 pmol/L] were fed eleven test meals (50g oral glucose with 0-30g doses of canola oil or whey protein) after an overnight fast. There were no significant FSI × fat (p=0.19) or FSI × protein (p=0.08) interaction effects on glucose response, suggesting that the effects of fat or protein on glycemia were independent of FSI of the subjects. In addition, the changes in relative glucose response per gram of fat (r = -0.05, p = 0.82) or protein (r = 0.08, p = 0.70) were not related to FSI of the subjects. In the second study, Healthy (FSI < 40pmol/L), Hyperinsulinemic (FSI ≥ 40pmol/L), and T2DM were fed five foods with 50g available carbohydrate. Among the subject-groups, the Glycemic Index (GI) values were not significantly different for each food, and the mean (±SEM) GI values of all foods were not significantly different (p>0.05). However, the mean (±SEM) Insulinemic Index of the foods was higher in T2DM (100±7, n=10) than those of Healthy (78±5, n=9) and Hyperinsulinemic subjects (70±5, n=12) (p=0.05). The Insulinemic Index was inversely associated with insulin sensitivity (r=-0.66, p<0.0001), positively related to fasting- and postprandial-glucose (both r=0.68, p<0.0001) and hepatic insulin extraction (r=0.62, p=0.0002). The oral-glucose data were pooled from the two studies to investigate whether there was any relationship between GLP-1 and insulin sensitivity, β-cell function and hepatic insulin extraction. No significant correlation was observed (p>0.05). The results suggest that the glucose-lowering effect of fat and protein is not affected by insulin sensitivity. GI is independent of the metabolic status of the subjects; however, unlike GI, Insulinemic Index is influenced by the metabolic status of the subjects, and thus may have limited clinical utility.

Proghrelin produces three proghrelin derived peptides (PGDP) known for their roles in glucose homeostasis: acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). Only the receptor for AG, growth hormone secretagogue receptor 1a (GHS R1a), is known, however there is evidence for additional receptors for AG, UAG and Ob. Our aim was to determine the actions of PGDP on two beta cell lines, MIN6 and INS-1, which we have shown to contain and lack GHS R1a respectively. PGDP increased proliferation in INS-1 but not MIN6 cells, measured by BrdU incorporation. AG decreased apopotosis in both cell lines, measured by decreased levels of activated caspase 3. Insulin secretion was investigated in INS-1 cells, where PGDP modulated insulin release in a glucose dependent manner. Our results indicate that PGDP modulate beta cell mass in the presence and absence of GHS R1a, and present a detailed anaylsis of insulin secretion in INS-1 cells.

No description available.

The purpose of this study was to determine if, after adjusting for the contribution of exercise dose, exercise intensity was associated with the improvement of insulin sensitivity. Abdominally obese, sedentary men (n = 16, [mean±SD] age: 45.0±7.5 yr; waist circumference: 108.6±5.3 cm) and women (n = 18, [mean±SD] age: 42.3±6.2 yr; waist circumference: 100.1±8.2 cm) performed daily, supervised exercise for 3 and 4 months, respectively. Exercising at a self selected exercise intensity, men were required to expend expended 700 kcal per session and women 500 kcal per session. Exercise intensity and dose were determined using heart rate and oxygen consumption data obtained from repeated graded exercise tests. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamp. Insulin sensitivity improved in both men and women (change score: men = 7.2±5.4 mg/kgskm/min, women = 5.8±7.1 mg/kgskm/min) (p < 0.05). Exercise intensity was associated with the improvements in insulin sensitivity in men (unstandardized regression coefficient (β) = 0.43, p = 0.02). Adjusting for exercise dose, the change in abdominal adipose tissue (AT), or the change visceral AT did not alter this association (p < 0.05). Exercise intensity was not associated with the improvement of insulin sensitivity in women (β = - 0.11, p = 0.7). Adjusting for exercise dose, the change in abdominal or visceral AT did not change the association in women (p > 0.05). Our findings suggest that exercise intensity is independently associated with the improvement of insulin sensitivity in abdominally obese men but not women. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2011-06-13 19:56:40.465

The goal of this study was to develop a model of the gastrointestinal tract (GIT) to be used for in vitro testing of oral insulin delivery devices. The method and intensity of mixing and effects of gastrointestinal fluids with and without enzymes were evaluated. Comparisons were made between an actively mixed simulator and a passively mixed simulator, where the actively mixed simulator is a magnetically stirred flask while the passively mixed simulator is a flexible container on a rocking stage. Slower mixing times and larger time constants for mixing were seen for the passively mixed simulator during a pH tracer experiment. Release studies were performed with several oral insulin delivery device models to evaluate the effects of different mixing techniques on insulin release. In all cases, the more intense mixing of the actively mixed simulator resulted in more insulin release. When using a nanoparticle model in intestinal fluid for example, 100% insulin release was observed in the actively mixed simulator while only 53% was released in the passively mixed simulator after 1 hour. Trypsin and pepsin were used to determine the ability of a drug delivery device to protect insulin from enzymatic degradation in which trypsin was added to simulated intestinal fluid and pepsin was added to simulated gastric fluid. Premature insulin release and insulin denaturation at body temperature occurred in the intestinal fluid so the protective effects against trypsin were unable to be effectively evaluated. An increase in insulin loss from 70% to 95% was detected in the presence of pepsin compared to gastric fluid without enzymes in the actively mixed simulator, indicating that acid hydrolysis of insulin as well as protease attack by pepsin will impact the behavior of an insulin delivery device. An improvement in insulin retention was observed in the passively mixed simulator. After 1 hour, insulin retained was increased from 4% in the actively mixed simulator to 10% in the passively mixed simulator, and after 2 hours, this increase was 2% to 7%. Premature insulin release from the delivery device, acid hydrolysis, temperature denaturation, and enzymatic degradation are factors limiting the effectiveness of oral insulin. / Thesis (Master, Chemical Engineering) -- Queen's University, 2011-08-19 19:29:52.804

No description available.

The literature comparing macronutrient metabolism in healthy and diabetic subjects is abundant; however, little data exists on how non-diabetic subjects with insulin resistance handle macronutrient. We did two studies to investigate the postprandial responses to macronutrient in healthy, hyperinsulinemic and type 2 diabetic (T2DM) subjects. In the first study, twenty-five healthy, non-diabetic subjects [9 with fasting serum insulin (FSI) <40pmol/L; 8 with 40 ≤ FSI < 70pmol/L; and 8 with FSI ≥ 70 pmol/L] were fed eleven test meals (50g oral glucose with 0-30g doses of canola oil or whey protein) after an overnight fast. There were no significant FSI × fat (p=0.19) or FSI × protein (p=0.08) interaction effects on glucose response, suggesting that the effects of fat or protein on glycemia were independent of FSI of the subjects. In addition, the changes in relative glucose response per gram of fat (r = -0.05, p = 0.82) or protein (r = 0.08, p = 0.70) were not related to FSI of the subjects. In the second study, Healthy (FSI < 40pmol/L), Hyperinsulinemic (FSI ≥ 40pmol/L), and T2DM were fed five foods with 50g available carbohydrate. Among the subject-groups, the Glycemic Index (GI) values were not significantly different for each food, and the mean (±SEM) GI values of all foods were not significantly different (p>0.05). However, the mean (±SEM) Insulinemic Index of the foods was higher in T2DM (100±7, n=10) than those of Healthy (78±5, n=9) and Hyperinsulinemic subjects (70±5, n=12) (p=0.05). The Insulinemic Index was inversely associated with insulin sensitivity (r=-0.66, p<0.0001), positively related to fasting- and postprandial-glucose (both r=0.68, p<0.0001) and hepatic insulin extraction (r=0.62, p=0.0002). The oral-glucose data were pooled from the two studies to investigate whether there was any relationship between GLP-1 and insulin sensitivity, β-cell function and hepatic insulin extraction. No significant correlation was observed (p>0.05). The results suggest that the glucose-lowering effect of fat and protein is not affected by insulin sensitivity. GI is independent of the metabolic status of the subjects; however, unlike GI, Insulinemic Index is influenced by the metabolic status of the subjects, and thus may have limited clinical utility.