Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 54-60).

Recent research suggests that amino acids can significantly increase skeletal muscle glucose uptake. However, the mechanism(s) have not been fully elucidated and it is also not clear if the beneficial impact amino acids have on healthy tissue translates to insulin resistant skeletal muscle. Therefore, in this series of studies, the effects of an amino acid mixture on glucose tolerance and insulin resistance were investigated. Study 1 Experiment-1 (Exp-1) demonstrated that an amino acid mixture significantly reduced the blood glucose response to an oral glucose challenge in Sprague Dawley rats. In Study 1 Exp-2, it was found that the improved glucose tolerance was due to an increase in skeletal muscle glucose uptake. The enhanced amino acid induced muscle glucose uptake was associated with improved cellular signaling. In Study 1 we could not determine the combined and/or individual effects of insulin and amino acids on glucose uptake, so in Study 2, the hindlimb of Sprague Dawley rats were perfused with glucose with or without amino acids in the presence and absence of insulin. Study 2, confirmed our previous findings that an amino acid mixture increased skeletal muscle glucose uptake compared to a carbohydrate supplement in the presence of insulin. The enhanced amino acid-stimulated glucose uptake was not due to increased phosphatidylinositol 3-kinase (PI 3-kinase) activity, although it was related to an increase in Akt substrate of 160 kDa (AS160) phosphorylation and a greater number of glucose transporters at the plasma membrane. In the final experiment, Study 3 investigated whether amino acids could improve glucose tolerance in an insulin resistant model. Study 3 Exp-1, demonstrated that an amino acid mixture significantly lowered the blood glucose response to an oral glucose challenge in obese Zucker rats. Study 3 Exp-2 showed that the improved glucose tolerance was due to enhanced amino acid induced skeletal muscle glucose uptake. Taken together, the results of this research suggests that adding an amino acid mixture to a carbohydrate supplement improves the blood glucose response to an oral glucose challenge, acutely lowers insulin resistance and this appears due to increased skeletal muscle glucose clearance and enhanced cellular signaling. / text

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No description available.

The purpose of this study was to analyze the experiences of self-monitoring of blood glucose (SMBG) usage of adults with type 2 diabetes mellitus (T2DM) who are not using insulin. The sample consisted of 11 women and 8 men who were Caucasian Americans, 38 to 79 years of age. Data were analyzed using the grounded theory method including open and axial coding and the constant comparative method. The theory of "SMBG as a Cue in T2DM Self-Care" emerged from the data and is composed of four categories (a) Engaging, (b) Checking, (c) Responding, and (d) Establishing a Pattern. Engaging marks the beginning of SMBG. Participants began on the recommendation of their physician and monitored between 2-6 times a day. Participants monitored because of curiosity and over time reduced or kept their initial frequency. Checking occurs when the blood glucose is obtained. Two subcategories emerged: Evaluating and Validating. The main items participants evaluated or validated were the effects of foods in relation to blood glucose levels. Responding involves reacting to SMBG. Two subcategories emerged: Taking Action and Experiencing Emotion. Most actions involved changing foods consumed. Participants described feeling conflicted and "being bad" when not following through with an action. Emotions such as blame and fear were experienced when blood glucose levels were higher than normal, while happiness was experienced with normal levels. Establishing a Pattern occurs when participants decide on how often to monitor. Two subcategories emerged: Using Regularly and Using Sporadically. The pattern developed was based on obtaining "normal" blood glucose patterns or on the absence of ill symptoms of T2DM. Healthcare provider disinterest in SMBG and fingertip pain contributed to a decreased monitoring frequency. Participants described cyclical, iterative episodes of Checking, Responding, and varying their established patterns throughout their experiences with monitoring. Participants discussed the value and struggles of SMBG in a T2DM self-care regimen. The theory of SMBG as a Cue in T2DM Self-Care could be used to guide the development of effective intervention strategies to help individuals with T2DM achieve blood glucose control which, in turn, leads to avoidance of ill symptoms and complications of T2DM.

No description available.

No description available.

Improved insulin sensitivity and glucose tolerance may be attributable to vitamin D sufficiency. An experimental design was created to investigate the use of phototherapy to increase serum vitamin D levels and improve circulating blood glucose levels in pre-diabetics. Seven participants with a pre-diabetic condition were randomly allocated to either 3 months of phototherapy or no therapy. OGTT, HbA1c, and serum vitamin D levels were assessed before and after treatment. In 2 treatment participants, pre-diabetes status was reduced from combined IFG/IGT to iIFG in one and iIGT in the second, while 1 control participant developed combined IFG/IGT and another, type 2 diabetes. HbA1c values improved in the phototherapy group but not in the controls. Phototherapy also increased serum vitamin D levels in the treatment group but not in the controls. This pilot study suggests that the experimental protocol was effective and it should be implemented in a larger sample size to confirm those trends.

The prevalence of obesity is increasing globally. Obesity is characterized by increased fat mass and is a risk factor for type 2 diabetes (T2D). Obesity is associated with hyperglycaemia, hyperinsulinemia, insulin resistance and chronic inflammation. Currently, the most effective and durable treatment for obesity and its comorbidities is bariatric surgery. Bariatric surgery changes food intake, energy balance and the composition of gut microbiota. Bariatric surgery can lower blood glucose and put T2D into remission. It was unknown if bariatric surgery-induced changes in the gut microbiota was an independent yet sufficient factor to lower blood glucose. Fecal microbiota transplantation (FMT) was performed on conventional (specific-pathogen-free, SPF) and germ-free (GF) mice using fecal material obtained from patients before surgery and 12 months after bariatric surgery. We tested FMT into mice from the same patients before and after vertical sleeve gastrectomy (VSL) and biliopancreatic diversion with duodenal switch (BPD/DS). FMT did not alter body weight, fat mass, glucose tolerance or glucose transporter mRNA expression in all intestine segments in SPF mice. FMT lowered blood glucose during an oral glucose load in GF mice receiving bacteria after VSL and BPD/DS bariatric surgery. Post-BPD/DS surgery FMT decreased Glut1 transcript level in the ileum and increased Glut1 transcript level in the TA muscle of GF mice, but did not change GLUT1 protein levels. Post-BPD/DS surgery FMT also decreased goblet cell count, villus height and crypt depth in the ileum of GF mice. We conclude that changes in the gut microbiota caused by bariatric surgery is a standalone factor that can lower blood glucose and alter gut morphology. / Thesis / Master of Science (MSc) / Type 2 diabetes is a chronic disease that involves high blood sugar (i.e. glucose), which can damage many parts of the body leading to serious complications. Diabetes is a growing global problem and is the seventh leading cause of death. Obesity is one of the largest factors leading to type 2 diabetes. Bariatric surgery reduces obesity and is to date the most effective method to lower blood glucose and reverse type 2 diabetes. Bariatric surgery alters gut anatomy and the types of bacteria that inhabit the gut. Gut bacteria can change obesity and blood glucose levels, but it was not known if the bacterial community present after bariatric surgery was a factor that is sufficient to lower blood glucose. We found that transferring gut bacteria from humans after bariatric surgery into mice lowers the blood glucose and alters the gut barrier structure where food is absorbed. It is not yet clear how this happens, but these findings show that a change in gut microbes is a standalone factor that can alter host blood glucose. Finding the glucose lowering factor in bacteria may be a new treatment to combat type 2 diabetes.

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