Matching Items (3)
Filtering by
- All Subjects: Insulin Resistance
- Creators: Herman, Richard
Description
Type II diabetes is a serious, chronic metabolic disease that has serious impacts on both the health and quality of life in patients diagnosed with the disease. Type II diabetes is also a very prevalent disease both in the United States and around the world. There is still a lot that is unknown about Type II diabetes, and this study will aim to answer some of these questions. The question posed in this study is whether insulin resistance changes as a function of time after the start of a high fat diet. We hypothesized that peripheral insulin resistance would be observed in animals placed on a high fat diet; and peripheral insulin resistance would have a positive correlation with time. In order to test the hypotheses, four Sprague-Dawley male rats were placed on a high fat diet for 8 weeks, during which time they were subjected to three intraperitonal insulin tolerance tests ((NovoLogTM 1 U/kg). These three tests were conducted at baseline (week 1), week 4, and week 8 of the high fat diet. The test consisted of serially determining plasma glucose levels via a pin prick methodology, and exposing a droplet of blood to the test strip of a glucometer (ACCUCHEKTM, Roche Diagnostics). Two plasma glucose baselines were taken, and then every 15 minutes following insulin injection for one hour. Glucose disposal rates were then calculated by simply dividing the glucose levels at each time point by the baseline value, and multiplying by 100. Area under the curve data was calculated via definite integral. The area under the curve data was then subjected to a single analysis of variance (ANOVA), with a statistical significance threshold of p<0.05. The results of the study did not indicate the development of peripheral insulin resistance in the animals placed on a high fat diet. Insulin-mediated glucose disposal was about 50% at 30 minutes in all four animals, during all three testing periods. Furthermore, the ANOVA resulted in p=0.92, meaning that the data was not statistically significant. In conclusion, peripheral insulin resistance was not observed in the animals, meaning no determination could be made on the relation between time and insulin resistance.
ContributorsBrown, Kellen Andrew (Author) / Caplan, Michael (Thesis director) / Herman, Richard (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function, and by inhibiting or activating LPL, respectively. Therefore, these proteins play key role in plasma lipid metabolism, but their role in regulating LPL activity in human insulin resistant (IR) (i.e., pre-diabetic) state is not known. Thus, the purpose of this research was to evaluate the concentrations of ApoC3 and ApoC2 in plasma along with the endothelial-bound LPL availability and activity in IR humans and in healthy, insulin sensitive (IS)/control humans. Insulin resistance was evaluated from plasma insulin and glucose responses to an oral glucose tolerance test, and by calculating the Matsuda index. Subjects were placed in the following groups: IR subjects, Matsuda index <4.0 (N=7; 4 males, 3 females); IS, Matsuda index >7.0 (N=11, 9 males, 2 females). IR and IS subjects received an intravenous infusion of insulin (1 mU/kg/min and 0.5 mU/kg/min, respectively) for 30 minutes to stimulate LPL activity. Whole-body endothelial-bound LPL was released from the vasculature by intravenous infusion of heparin. Plasma samples were collected 10 minutes after heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations. Although plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P = 0.02), plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03). However, ApoC2 concentration was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). These findings suggest that circulating APOC3 and ApoC2 are not key determinants regulating LPL activity during hyperinsulinemia in the vasculature of insulin resistant humans.
ContributorsJohnsson, Kailin Alexis (Author) / Katsanos, Christos (Thesis advisor) / Herman, Richard (Committee member) / De Filippis, Elena (Eleanna) (Committee member) / Arizona State University (Publisher)
Created2023
Description
In post-industrialized societies, increased consumption of fat-rich diets has been correlated to increasing rates of metabolic disorders, such as Type II Diabetes, which is further linked to insulin resistance. Due to this modern epidemic, it has become exceedingly important to learn more about these disorders with the ultimate goal of developing more effective treatments. With an overall focus on insulin resistance, the main purposes of this study were to (1) differentiate between two types of insulin resistance and their corresponding measurements and to (2) demonstrate metabolic changes that occur in response to overconsumption of a calorically dense diet. This was accomplished over a 23-week timespan by applying statistical analysis to periodically measured fasting insulin and blood glucose levels in rats fed either a high fat diet or low fat (chow) diet. Body weights were also recorded. The results of this study showed that rats fed a high fat diet experienced fasting hyperinsulinemia, hyperglycemia, and insulin resistance compared to rats fed a chow diet, and that the homeostatic model assessment (HOMA) scale and insulin-stimulated glucose disposal (ISGD) measure different types of insulin resistance. This study was unique in the fact that hepatic insulin resistance and peripheral insulin resistance were differentiated in the same rat.
ContributorsHenry, Lauren Elizabeth (Author) / Herman, Richard (Thesis director) / Baluch, Debra (Committee member) / School of Life Sciences (Contributor) / School of Music (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05