Browsing by Subject "insulin"

Now showing 1 - 5 of 5
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    Chronic and Acute Effects of Green Tea Extract and Catechol-O-methyltransferase Genotype on Body Composition and Obesity-Associated Hormones in Overweight and Obese Postmenopausal Women
    (2015-06) Dostal, Allison
    This dissertation details the chronic and acute effects of green tea extract (GTE) supplementation (1315 mg green tea catechins/day, 843 mg as (-)-epigallocatechin-3-gallate, [EGCG]) on body composition, obesity-associated hormones, glucose homeostasis, and satiety in overweight and obese postmenopausal women at increased risk for breast cancer due to high mammographic density. Participants in the forthcoming studies were a subset of participants drawn from the Minnesota Green Tea Trial (MGTT), which was a randomized, placebo-controlled, double-blind, phase II clinical trial designed to determine the effects of supplementing GTE for one year on breast cancer risk factors including mammographic density, reproductive hormones, insulin-like growth factor (IGF) axis proteins, and F2-isoprostanes, a recognized biomarker of oxidative stress. Effect modification by catechol-O-methyltransferase (COMT), an enzyme involved in the metabolism of green tea catechins, estrogens, and norepinephrine, was also analyzed for all endpoints, due to its potential role in modulating the impact of GTE on breast cancer risk factors. Chapter 1 provides a brief introduction to the MGTT and the forthcoming chapters. Chapter 2 presents a review of the literature, providing context for the MGTT and ancillary studies. Chapter 3 describes the effect of GTE on anthropometric variables, obesity-associated hormones (leptin, ghrelin, adiponectin, and insulin) and markers of glucose homeostasis (blood glucose concentrations and the homeostasis measure of insulin resistance [HOMA-IR]) in 237 participants. In this study, no changes in energy intake or anthropometric measurements were observed in women taking GTE or placebo. Similarly, no changes were seen in circulating leptin, ghrelin, adiponectin, or glucose concentrations. However, among participants with baseline insulin ≥10 µIU/mL, there was a reduction in insulin concentration in the GTE group over 12 months compared to the placebo group and participants with baseline insulin < 10 µIU/mL in either group (P < 0.01). Participants with the homozygous high-activity (G/G) form of COMT showed significantly lower adiponectin and higher insulin concentrations at month 12 as compared to those with the low-activity (A/A) genotype, regardless of treatment group. Chapter 4 describes the more specific effects of GTE on body composition as measured by dual-energy x-ray absorptiometry (DXA), including total body fat, % body fat, region-specific adiposity, and bone mineral density (BMD) in 121 participants. These results were correlated with measures of leptin, adiponectin, and insulin. No changes in BMI, total fat mass, % body fat, or BMD were observed in women taking GTE compared to placebo; however, a reduction in visceral adipose tissue mass in GTE participants as compared to the placebo group nearly reached significance. Interactions were observed between treatment, time, and baseline BMI for gynoid % fat and tissue % fat, with more favorable results seen in the GTE group. No changes were seen in circulating leptin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. Chapter 5 details the acute postprandial effects of GTE administration in 60 participants who were administered a high-carbohydrate breakfast meal in the final months of their participation in the MGTT. Leptin, ghrelin, and adiponectin were not different between GTE and placebo at any time point and COMT genotype did not modify these results. Participants randomized to GTE with the high-activity form of the COMT enzyme (GTE-high COMT) had higher insulin concentrations immediately after the test meal (time 0) and at 0.5 and 1.0 hours post-meal compared to all COMT groups randomized to placebo. The GTE-high COMT group had higher insulin concentrations at times 0, 0.5, 1.0, 1.5, and 2.0 h compared to the GTE-low COMT group. Nine markers of satiety and appetite, as measured through comparison of mean area under the curve (cm/hr), were not different between GTE and placebo. The results of these three studies demonstrate that daily supplementation of 1315 mg GTE, independent of caffeine, does not influence long-term energy intake, satiety, body weight, or obesity-associated hormones, though it may be beneficial for individuals with a higher degree of visceral adiposity and with increased circulating insulin concentrations. This suggests benefit for those at risk for metabolic syndrome or type 2 diabetes. Given the association of these conditions with breast cancer risk, GTE may be a beneficial dietary supplement for overweight and obese postmenopausal women.
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    Diabetes and Your Future Health
    (2009-05-04) Vlaminck, Jay
    In patients with poorly controlled insulin dependent type 2 diabetes, addition of metformin to insulin regimen significantly lowers hemoglobin A1c levels and results in lower units of insulin needed per day than in patients receiving insulin alone. There is also a trend towards decreased weight gain in those receiving insulin + metformin, though this was not found to be statistically significant in this study.
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    Diabetes Management After Failed Glycemic Control on Metformin
    (2009-09-18) Huseby, Krysta
    Many patients with type 2 diabetes are initially treated with metformin, but after a while, metformin alone may not be enough to control their blood sugars. This is a patient guide describing different medications a patient might add on to metformin to get better control.
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    Forage quality and blood metabolites of horses grazing alfalfa, cool-season perennial grass, and teff
    (2018-07) DeBoer, Michelle
    The impact of forage species on blood metabolites concentrations of grazing horses (Equus caballus L.) is unknown. However, these differences can be crucial as plasma amino acid (AA) concentrations as well as the glucose and insulin response of grazing horses can be indicators of nutritional status or metabolic health. As a result, the objectives of these studies were to determine the impact of different forage species on plasma AA concentrations, protein synthesis, as well as the glucose and insulin response across seasons. Research was conducted in May (spring), July (summer), September (fall), and late October (late-fall) in St. Paul, MN in 2016. However, the data collected was divided into three different studies (1) July samples taken during the first 4 hours were used to evaluate the forage and plasma AA concentrations (2) samples collected in July and September were included in the glucose and insulin response analysis of the regular grazing season and (3) May and October samples were used to analyze the glucose and insulin response during the extended grazing season. Forage treatments included alfalfa (Medicago sativa L.), a mixed perennial cool-season grass (CSG) and teff (Eragrostis tef [Zucc.] Trotter), however, not all forage species were grazed every season. Alfalfa and CSG were grazed in May while CSG and teff were grazed during the October, with all three species grazed in July and September. During these times, forages were grazed by six horses (24 ± 2 yr) randomly assigned to a forage in either a Latin-square or cross-over design. Jugular catheters were inserted 1 h prior to the start of grazing and horses had access to pasture starting at 08:00 h for either 4 or 8 h depending on the season. Jugular venous blood samples were collected from each horse prior to being turned out (0 h) and then at 2 hour intervals following turnout. Plasma and serum samples were collected and analyzed for AA, glucose, and insulin. Corresponding forage samples were taken by hand harvest. Equine muscle satellite cell cultures were treated with sera from grazing horses to assess de novo protein synthesis. Seasons were analyzed separately and data were analyzed using the MIXED procedure in SAS with P ≤ 0.05. When evaluating forage, AA were generally lowest in teff and highest in CSG (P ≤ 0.05). Significant differences in threonine concentration in the plasma were observed; there was no effect on de novo protein synthesis of cultured equine myotubes treated with plasma obtained from the grazing horses (P ≥ 0.20). As a result, although there were significant differences in forage AA content only plasma threonine concentration was different at 4 h with no effect on protein synthesis of cultured equine satellite cells. When evaluating the glucose and insulin response during the regular grazing season, teff generally had lower (P ≤ 0.05) equine digestible energy (DE), crude protein (CP) and nonstructural carbohydrates (NSC) compared to the other forages. Differences in peak insulin were observed between horses grazing CSG and teff during the fall grazing (P ≤ 0.05). Additionally, when evaluating the extended grazing season, teff had lower NSC than CSG in the late-fall (P ≤ 0.05) with subsequently lower average glucose, average insulin, and peak insulin in horses grazing teff compared to CSG (P ≤ 0.05).These results suggest grazing teff could lower the glucose and insulin response of some horses, specifically in the fall and late-fall, and may provide an alternative forage for horses with metabolic concerns,
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    Programmed death-1 regulates islet-specific lymphocytes in type 1 diabetes
    (2018-12) Martinov, Tijana
    Programmed death-1 (PD-1) is a T cell inhibitory receptor important for tolerance maintenance. PD-1 is highly expressed on chronically stimulated T cells, such as those specific for persistent viral or tumor antigens. PD-1 pathway blockade revolutionized cancer therapy in recent years. While response rates are higher than with chemotherapy, not all patients respond, and some develop autoimmune-like symptoms, or even overt autoimmunity. Herein, I sought to understand how the PD-1 pathway regulated islet-specific CD4+ T cells during type 1 diabetes (T1D) progression in non-obese diabetic (NOD) mice. Since insulin itself is one of the main antigens driving T1D, we developed insulin peptide:MHCII tetramer reagents to track insulin-reactive CD4+ T cells. Insulin-specific CD4+ T cells that expressed the most PD-1 also had the highest affinity for self, suggesting that PD-1 preferentially regulated those cells with the highest autoimmune potential. In NOD mice, the majority of insulin-specific CD4+ T cells had an anergic (tolerant) phenotype, but surprisingly, PD-1 blockade did not override the anergy program. These findings suggested that the differentiation state of the CD4+ T cell pre-determine its susceptibility to PD-1 blockade. Autoantibody production is a hallmark of autoimmunity, and has also been reported in patients treated with PD-1 blockade, suggesting that PD-1 might regulate this process. Autoantibody production results from B cell:CD4+ T cell interactions in the germinal center of the lymph node. The dynamics and regulation of the germinal center in spontaneous autoimmunity and after PD-1 blockade are not well understood, primarily due to an inability to track self-specific lymphocytes. To bridge this knowledge gap, we used tetramers to phenotype islet-specific CD4+ T cells and B cells in mice. PD-1- or PD-L1-deficient mice, as well as NOD mice treated with anti-PD-1, had increased insulin autoantibodies, as well as increased insulin-specific T follicular helper CD4+ T cells and germinal center B cells compared to controls. This increase was dependent on CD4+ T cell-intrinsic PD-1 signaling and relied on peptide:MHCII recognition. Taken together, my thesis work provides a mechanistic explanation for autoantibody onset following PD-1 blockade in the clinic, and has important implications for cancer immunotherapy and autoimmunity.