Cellular modeling : insight into oral minimal models of insulin secretion 1

21 The oral glucose tolerance test (OGTT) and meal tolerance test are common clinical tests of the 22 glucose-insulin system. Several mathematical models have been suggested as means to extract 23 information about beta-cell function from data from oral tolerance tests. Any such model needs 24 necessarily to be fairly simple but should at the same time be linked to the underlying biology of the 25 insulin secreting beta-cells. The scope of the present work is to present a way to make such a 26 connection using a recent model describing intracellular mechanisms. We show how the three main 27 components of oral minimal secretion models, derivative control, proportional control and delay, 28 are related to subcellular events, thus providing mechanistic underpinning of the assumptions of the 29 minimal models. 30 31