Question

analyze the relationship between normal physiology and pathological phenomena in diabetes type 2 produced by altered states across the life span. Discuss implications. Give an example to illustrate your comparison.

Answer 1

Normal regulation of glucose metabolism is determined by a feedback loop involving the islet β-cell and insulin-sensitive tissues in which tissue sensitivity to insulin determines the magnitude of the β-cell response. When insulin resistance is present, the β-cell maintains normal glucose tolerance by increasing insulin output. It is only when the β-cell is incapable of releasing sufficient insulin in the presence of insulin resistance that glucose levels rise. While β-cell dysfunction has a clear genetic component, environmental changes play a vital role. Modern approaches have also informed regarding the importance of hexoses, amino acids and fatty acids in determining insulin resistance and β-cell dysfunction as well as the potential role of alterations in the microbiome. A number of new treatment approaches have been developed, but more effective therapies that slow the progressive loss of β-cell function are needed. Recent clinical trials have provided important information regarding approaches to prevent and treat type 2 diabetes as well as some of the adverse effects of these interventions. However, additional long-term studies of medications and bariatric surgery are required in order to identify novel approaches to prevention and treatment, thereby reducing the deleterious impact of type 2 diabetes.

Pathological phenomena in Type 2 diabetes

Development of the insulin radioimmunoassay led to the identification that individuals with “early maturity onset diabetes” produced insulin and secreted this hormone in response to nutrient ingestion. Subsequently, individuals manifest a defect in the ability of the islet β-cell to respond to intravenous secretagogues including glucose.

In these earlier days it was demonstrated that these individuals also did not respond well to insulin and were thus deemed to be “insulin-insensitive”. It was subsequently shown that this contributed to increased glucose production by the liver and decreased glucose uptake in muscle and adipose tissue5. Today we recognize that a proportion of these abnormalities are explained by adiposity, especially that located within the intra-abdominal cavity.

Insulin released in response to β-cell stimulation mediates the uptake of glucose, amino acids and fatty acids by insulin-sensitive tissues. In turn, these tissues feedback information to the islet regarding their need for insulin, the mediator of which has not yet been identified but is likely to involve integration between the brain and humoral systems. When insulin resistance is present, as seen most commonly with obesity, the β-cell increases its insulin output to maintain normal glucose tolerance . However, when the β-cell is incapable of this task, the result is an elevation in plasma glucose