Modelling the effects of glucagon during glucose tolerance testing.

From Europe PMC via Jisc Publications RouterHistory: ppub 2019-12-01, epub 2019-12-12Publication status: PublishedBACKGROUND:Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. RESULTS:Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). CONCLUSIONS:The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance

Remote Sensing Analysis of Vegetation Recovery following Short-Interval Fires in Southern California Shrublands

Increased fire frequency has been shown to promote alien plant invasions in the western United States, resulting in persistent vegetation type change. Short interval fires are widely considered to be detrimental to reestablishment of shrub species in southern California chaparral, facilitating the invasion of exotic annuals and producing "type conversion". However, supporting evidence for type conversion has largely been at local, site scales and over short post-fire time scales. Type conversion has not been shown to be persistent or widespread in chaparral, and past range improvement studies present evidence that chaparral type conversion may be difficult and a relatively rare phenomenon across the landscape. With the aid of remote sensing data covering coastal southern California and a historical wildfire dataset, the effects of short interval fires (<8 years) on chaparral recovery were evaluated by comparing areas that burned twice to adjacent areas burned only once. Twelve pairs of once- and twice-burned areas were compared using normalized burn ratio (NBR) distributions. Correlations between measures of recovery and explanatory factors (fire history, climate and elevation) were analyzed by linear regression. Reduced vegetation cover was found in some lower elevation areas that were burned twice in short interval fires, where non-sprouting species are more common. However, extensive type conversion of chaparral to grassland was not evident in this study. Most variables, with the exception of elevation, were moderately or poorly correlated with differences in vegetation recovery