Time-dependent Mechanisms in Beta-cell Glucose Sensing

The relation between plasma glucose and insulin release from pancreatic beta-cells is not stationary in the sense that a given glucose concentration leads to a specific rate of insulin secretion. A number of time-dependent mechanisms appear to exist that modify insulin release both on a short and a longer time scale. Typically, two phases are described. The first phase, lasting up to 10 min, is a pulse of insulin release in response to fast changes in glucose concentration. The second phase is a more steady increase of insulin release over minutes to hours, if the elevated glucose concentration is sustained. The paper describes the glucose sensing mechanism via the complex dynamics of the key enzyme glucokinase, which controls the first step in glucose metabolism: phosphorylation of glucose to glucose-6-phosphate. Three time-dependent phenomena (mechanisms) are described. The fastest, corresponding to the first phase, is a delayed negative feedback regulating the glucokinase activity. Due to the delay, a rapid glucose increase will cause a burst of activity in the glucose sensing system, before the glucokinase is down-regulated. The second mechanism corresponds to the translocation of glucokinase from an inactive to an active form. As the translocation is controlled by the product(s) of the glucokinase reaction rather than by the substrate glucose, this mechanism gives a positive, but saturable, feedback. Finally, the release of the insulin granules is assumed to be enhanced by previous glucose exposure, giving a so-called glucose memory to the beta-cells. The effect depends on the insulin release of the cells, and this mechanism constitutes a second positive, saturable feedback system. Taken together, the three phenomena describe most of the glucose sensing behaviour of the beta-cells. The results indicate that the insulin release is not a precise function of the plasma glucose concentration. It rather looks as if the beta-cells just increase the insulin production, until the plasma glucose has returned to normal. This type of integral control has the advantage that the precise glucose sensitivity of the beta-cells is not important for normal glucose homeostasis

Development and evaluation of a quality assessment instrument for occupational physicians

OBJECTIVES: To develop and apply a method for assessing the quality of the process of occupational health care for individual patients. METHODS: The scientific literature was studied to develop a method to assess the quality of the process of occupational rehabilitation for workers with low back pain. The method was applied to health care and university workers with low back pain who were rehabilitated by their occupational physicians. RESULTS: Assessment of quality of care is regarded as a four step approach. Firstly, guidelines should be developed and implemented. Secondly, indicators for quality and criteria to demarcate good and deviant quality were derived from the guidelines. Thirdly, a method for data collection was chosen. Finally, quality was scored. For occupational rehabilitation, there was some deviance from the guidelines for most cases, especially in continuity of care with a deviant rate of 47%. Other indicators deviated from 1.4%- 17.4%. Occupational physicians agreed on the relevance of the indicators and criteria, but for three indicators they evaluated the criteria as too rigid. They did not agree with their own performance scores in 66% of the deviant cases. CONCLUSION: Assessing the quality of the process of occupational health care with this method is an asset to present methods, but more specific criteria are needed for a more sensitive assessment.